首页 > 最新文献

Journal of Immunotherapy最新文献

英文 中文
Taurine Inhibits Lung Metastasis in Triple-Negative Breast Cancer by Modulating Macrophage Polarization Through PTEN-PI3K/Akt/mTOR Pathway. 牛磺酸通过 PTEN-PI3K/Akt/mTOR 通路调节巨噬细胞极化抑制三阴性乳腺癌的肺转移
IF 3.9 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-17 DOI: 10.1097/CJI.0000000000000518
Yufeng Lin, Yongtong Huang, Yifan Zheng, Wanting Chen, Yongcheng Zhang, Yongxia Yang, Wenbin Huang
SUMMARYTaurine (Tau) has been found to inhibit triple-negative breast cancer (TNBC) invasion and metastasis. However, its effect on tumor-promoting macrophages and tumor suppressor macrophages in breast cancer progression remains unknown. In this study, we investigated the effects of Tau on macrophage polarization and its role in TNBC cell growth, invasion, and metastasis. We induced human THP-1 monocytes to differentiate into M2 macrophages through exogenous addition of interleukin-4. We used the TNBC cell lines MDA-MB-231 and BT-549 cultured in a conditioned medium from M2 macrophages to investigate the effect of Tau on tumor growth and invasion. We analyzed macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression by quantitative polymerase chain reaction. We also detected the PTEN-PI3K/Akt/mTOR signaling pathway that mediates M1 macrophage to suppress tumor invasion using western blotting. Our results showed that Tau inhibits breast cancer metastasis to the lungs in vivo and cell invasion by altering the polarization of tumor-associated macrophage in vitro. In addition, Tau can up-regulate PTEN expression, suppress the PI3K-Akt signaling pathway, and promote the M1 polarization of macrophages, which ultimately inhibits the metastasis of TNBC cells. Our findings suggest that Tau inhibits the activation of the PI3K-Akt-mTOR signaling pathway by up-regulating PTEN, promotes the proportion of M1 macrophages in tumor-associated macrophage, and suppresses the invasion and metastasis of TNBC. This provides a potential therapeutic approach to influence cancer progression and metastasis.
摘要已发现牛磺酸(Tau)可抑制三阴性乳腺癌(TNBC)的侵袭和转移。然而,它对乳腺癌进展过程中肿瘤促进巨噬细胞和肿瘤抑制巨噬细胞的影响仍然未知。在本研究中,我们研究了 Tau 对巨噬细胞极化的影响及其在 TNBC 细胞生长、侵袭和转移中的作用。我们通过外源性添加白细胞介素-4诱导人THP-1单核细胞分化为M2巨噬细胞。我们使用在M2巨噬细胞条件培养基中培养的TNBC细胞系MDA-MB-231和BT-549来研究Tau对肿瘤生长和侵袭的影响。我们通过定量聚合酶链反应分析了巨噬细胞亚群分布、M1和M2巨噬细胞相关标记物以及mRNA表达。我们还利用Western印迹技术检测了介导M1巨噬细胞抑制肿瘤侵袭的PTEN-PI3K/Akt/mTOR信号通路。我们的研究结果表明,Tau能在体内抑制乳腺癌向肺部的转移,并在体外通过改变肿瘤相关巨噬细胞的极化来抑制细胞侵袭。此外,Tau还能上调PTEN的表达,抑制PI3K-Akt信号通路,促进巨噬细胞的M1极化,最终抑制TNBC细胞的转移。我们的研究结果表明,Tau通过上调PTEN抑制PI3K-Akt-mTOR信号通路的激活,促进肿瘤相关巨噬细胞中M1巨噬细胞的比例,抑制TNBC的侵袭和转移。这为影响癌症进展和转移提供了一种潜在的治疗方法。
{"title":"Taurine Inhibits Lung Metastasis in Triple-Negative Breast Cancer by Modulating Macrophage Polarization Through PTEN-PI3K/Akt/mTOR Pathway.","authors":"Yufeng Lin, Yongtong Huang, Yifan Zheng, Wanting Chen, Yongcheng Zhang, Yongxia Yang, Wenbin Huang","doi":"10.1097/CJI.0000000000000518","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000518","url":null,"abstract":"SUMMARY\u0000Taurine (Tau) has been found to inhibit triple-negative breast cancer (TNBC) invasion and metastasis. However, its effect on tumor-promoting macrophages and tumor suppressor macrophages in breast cancer progression remains unknown. In this study, we investigated the effects of Tau on macrophage polarization and its role in TNBC cell growth, invasion, and metastasis. We induced human THP-1 monocytes to differentiate into M2 macrophages through exogenous addition of interleukin-4. We used the TNBC cell lines MDA-MB-231 and BT-549 cultured in a conditioned medium from M2 macrophages to investigate the effect of Tau on tumor growth and invasion. We analyzed macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression by quantitative polymerase chain reaction. We also detected the PTEN-PI3K/Akt/mTOR signaling pathway that mediates M1 macrophage to suppress tumor invasion using western blotting. Our results showed that Tau inhibits breast cancer metastasis to the lungs in vivo and cell invasion by altering the polarization of tumor-associated macrophage in vitro. In addition, Tau can up-regulate PTEN expression, suppress the PI3K-Akt signaling pathway, and promote the M1 polarization of macrophages, which ultimately inhibits the metastasis of TNBC cells. Our findings suggest that Tau inhibits the activation of the PI3K-Akt-mTOR signaling pathway by up-regulating PTEN, promotes the proportion of M1 macrophages in tumor-associated macrophage, and suppresses the invasion and metastasis of TNBC. This provides a potential therapeutic approach to influence cancer progression and metastasis.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140693988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical Manifestation, Risk Factors, and Immune Checkpoint Inhibitor Rechallenge of Checkpoint Inhibitor-Associated Pneumonitis in Patients With Lung Cancer. 肺癌患者检查点抑制剂相关肺炎的临床表现、风险因素和免疫检查点抑制剂再挑战
IF 3.9 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-15 DOI: 10.1097/CJI.0000000000000515
Xuemeng Li, Fang Yang, Baogang Liu, Leiguang Ye, Jingwen Du, Xiaona Fan, Yue Yu, Mengwei Li, Li Bu, Zhuoqi Zhang, Lili Xie, Wuquan Li, Jiaqing Qi
SUMMARYImmune-related adverse effects can lead to damage to various systems of the body, checkpoint inhibitor-associated pneumonitis (CIP) is one of the potentially lethal immune-related adverse effects. However, evidence regarding the risk factors associated with CIP is limited. To timely and accurate identification and prompt treatment of CIP, understanding the risk factors for multimorbidity among diverse study populations becomes crucial. We retrospectively analyzed the clinical data of 1131 patients with lung cancer receiving immunotherapy to identify 110 patients with CIP, the clinical characteristics and radiographic features of patients with CIP were analyzed. A case-control study was subsequently performed to identify the risk factors of CIP. The median treatment cycle was 5 cycles and the median time to onset of CIP was 4.2 months. CIP was mainly grade I or II. Most cases improved after discontinuation of immune checkpoint inhibitors (ICIs) or hormone therapy. Severe CIP tended to occur earlier in comparison to mild to moderate cases. The recurrence rate was 20.6% in ICI-rechallenged patients, and patients with relapsed CIP were usually accompanied by higher-grade adverse events than at first onset. Among the 7 patients with relapse, ICI-associated deaths occurred in 2 patients (28.6%). For rechallenging with ICIs after recovery from CIP, caution should be practiced. Male [odds ratio (OR): 2.067; 95% CI: 1.194-3.579; P= 0.009], history of chest radiation (OR: 1.642; 95% CI: 1.002-2.689; P= 0.049) and underlying lung disease (OR: 2.347; 95% CI: 1.008-5.464; P=0.048) was associated with a higher risk of CIP.
摘要免疫相关不良反应可导致身体各系统受损,检查点抑制剂相关肺炎(CIP)是潜在的致命性免疫相关不良反应之一。然而,有关CIP相关风险因素的证据还很有限。为了及时、准确地识别并迅速治疗 CIP,了解不同研究人群的多病风险因素至关重要。我们回顾性分析了1131名接受免疫治疗的肺癌患者的临床数据,从中发现了110名CIP患者,并分析了CIP患者的临床特征和影像学特征。随后进行了病例对照研究,以确定CIP的风险因素。中位治疗周期为5个周期,CIP发病的中位时间为4.2个月。CIP主要为I级或II级。大多数病例在停用免疫检查点抑制剂(ICIs)或激素治疗后病情有所好转。与轻度和中度病例相比,重度CIP往往发生得更早。接受过ICI治疗的患者复发率为20.6%,复发的CIP患者通常伴有比初发患者更严重的不良反应。在 7 名复发患者中,有 2 名患者(28.6%)因 ICI 而死亡。在 CIP 康复后再次使用 ICI 时应谨慎。男性[几率比(OR):2.067;95% CI:1.194-3.579;P= 0.009]、胸部放射史(OR:1.642;95% CI:1.002-2.689;P= 0.049)和潜在肺部疾病(OR:2.347;95% CI:1.008-5.464;P=0.048)与较高的 CIP 风险相关。
{"title":"Clinical Manifestation, Risk Factors, and Immune Checkpoint Inhibitor Rechallenge of Checkpoint Inhibitor-Associated Pneumonitis in Patients With Lung Cancer.","authors":"Xuemeng Li, Fang Yang, Baogang Liu, Leiguang Ye, Jingwen Du, Xiaona Fan, Yue Yu, Mengwei Li, Li Bu, Zhuoqi Zhang, Lili Xie, Wuquan Li, Jiaqing Qi","doi":"10.1097/CJI.0000000000000515","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000515","url":null,"abstract":"SUMMARY\u0000Immune-related adverse effects can lead to damage to various systems of the body, checkpoint inhibitor-associated pneumonitis (CIP) is one of the potentially lethal immune-related adverse effects. However, evidence regarding the risk factors associated with CIP is limited. To timely and accurate identification and prompt treatment of CIP, understanding the risk factors for multimorbidity among diverse study populations becomes crucial. We retrospectively analyzed the clinical data of 1131 patients with lung cancer receiving immunotherapy to identify 110 patients with CIP, the clinical characteristics and radiographic features of patients with CIP were analyzed. A case-control study was subsequently performed to identify the risk factors of CIP. The median treatment cycle was 5 cycles and the median time to onset of CIP was 4.2 months. CIP was mainly grade I or II. Most cases improved after discontinuation of immune checkpoint inhibitors (ICIs) or hormone therapy. Severe CIP tended to occur earlier in comparison to mild to moderate cases. The recurrence rate was 20.6% in ICI-rechallenged patients, and patients with relapsed CIP were usually accompanied by higher-grade adverse events than at first onset. Among the 7 patients with relapse, ICI-associated deaths occurred in 2 patients (28.6%). For rechallenging with ICIs after recovery from CIP, caution should be practiced. Male [odds ratio (OR): 2.067; 95% CI: 1.194-3.579; P= 0.009], history of chest radiation (OR: 1.642; 95% CI: 1.002-2.689; P= 0.049) and underlying lung disease (OR: 2.347; 95% CI: 1.008-5.464; P=0.048) was associated with a higher risk of CIP.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140700753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multiple Eruptive Keratoacanthomas Secondary to Nivolumab Immunotherapy. 纳武单抗免疫治疗继发的多发发疹性角膜棘瘤。
IF 3.9 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-01 Epub Date: 2023-11-27 DOI: 10.1097/CJI.0000000000000498
Eric Olsen, Steven A Svoboda, Marjorie Montanez-Wiscovich, Sami K Saikaly

Immune checkpoint inhibitors are increasingly being utilized for the treatment of advanced neoplastic disease and have been associated with wide-ranging cutaneous adverse effects. Though exceedingly rare, eruptive keratoacanthomas have been associated with the use of immune checkpoint inhibitors such as pembrolizumab and nivolumab, whose molecular target is the programmed cell death protein 1. Herein, we detail a case of numerous eruptive keratoacanthomas arising in a patient one month after initiation of nivolumab for recurrent metastatic oropharyngeal squamous cell carcinoma. Treatment with multiple rounds of intralesional corticosteroids and a several-month course of oral acitretin resulted in partial improvement. Subsequent treatment with intralesional 5-fluorouracil demonstrated near-complete resolution of the keratoacanthomas without discontinuation of nivolumab. Although eruptive keratoacanthomas secondary to immune checkpoint inhibitors are exceptionally rare, physicians should be aware of this cutaneous adverse effect as their use becomes more widespread.

免疫检查点抑制剂越来越多地被用于晚期肿瘤疾病的治疗,并与广泛的皮肤不良反应有关。虽然极为罕见,但爆发性角棘瘤与免疫检查点抑制剂的使用有关,如派姆单抗和纳武单抗,其分子靶点是程序性细胞死亡蛋白1。在这里,我们详细介绍了一个病例的大量爆发角棘瘤出现在一个月后的病人开始纳伏单抗复发转移口咽鳞状细胞癌。多轮局部皮质类固醇治疗和几个月的口服阿维素治疗可部分改善。随后的局部5-氟尿嘧啶治疗显示,在没有停止纳武单抗的情况下,角膜棘瘤几乎完全消退。虽然继发于免疫检查点抑制剂的爆发性角棘瘤非常罕见,但随着它们的使用越来越广泛,医生应该意识到这种皮肤不良反应。
{"title":"Multiple Eruptive Keratoacanthomas Secondary to Nivolumab Immunotherapy.","authors":"Eric Olsen, Steven A Svoboda, Marjorie Montanez-Wiscovich, Sami K Saikaly","doi":"10.1097/CJI.0000000000000498","DOIUrl":"10.1097/CJI.0000000000000498","url":null,"abstract":"<p><p>Immune checkpoint inhibitors are increasingly being utilized for the treatment of advanced neoplastic disease and have been associated with wide-ranging cutaneous adverse effects. Though exceedingly rare, eruptive keratoacanthomas have been associated with the use of immune checkpoint inhibitors such as pembrolizumab and nivolumab, whose molecular target is the programmed cell death protein 1. Herein, we detail a case of numerous eruptive keratoacanthomas arising in a patient one month after initiation of nivolumab for recurrent metastatic oropharyngeal squamous cell carcinoma. Treatment with multiple rounds of intralesional corticosteroids and a several-month course of oral acitretin resulted in partial improvement. Subsequent treatment with intralesional 5-fluorouracil demonstrated near-complete resolution of the keratoacanthomas without discontinuation of nivolumab. Although eruptive keratoacanthomas secondary to immune checkpoint inhibitors are exceptionally rare, physicians should be aware of this cutaneous adverse effect as their use becomes more widespread.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of PTPN3 Expressed in Activated Lymphocytes Enhances the Antitumor Effects of Anti-PD-1 Therapy in Head and Neck Cancer, Especially in Hypoxic Environments. 抑制活化淋巴细胞中表达的 PTPN3 可增强头颈癌中抗 PD-1 疗法的抗肿瘤效果,尤其是在缺氧环境中。
IF 3.9 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-01 Epub Date: 2024-02-01 DOI: 10.1097/CJI.0000000000000503
Shogo Masuda, Hideya Onishi, Naoya Iwamoto, Akira Imaizumi, Satoko Koga, Shinjiro Nagao, Keita Sakanashi, Shinsaku Itoyama, Akiko Fujimura, Noritaka Komune, Ryunosuke Kogo, Masayo Umebayashi, Takashi Morisaki, Takashi Nakagawa

In the tumor microenvironment, wherein cytotoxic lymphocytes interact with cancer cells, lymphocyte exhaustion, an immune checkpoint inhibitor target, is promoted. However, the efficacy of these inhibitors is limited, and improving response rates remains challenging. We previously reported that protein tyrosine phosphatase nonreceptor type (PTPN) 3 is a potential immune checkpoint molecule for activated lymphocytes and that PTPN3 inhibition should be a focus area for cancer immunotherapy development. Therefore, in this study, we focused on PTPN3-suppressive therapy in terms of lymphocyte exhaustion under hypoxic conditions, which are a cancer microenvironment, and investigated measures for improving the response to anti-programmed death receptor (PD)-1 antibody drugs. We found that PTPN3 expression was upregulated in activated lymphocytes under hypoxic conditions, similar to the findings for other immune checkpoint molecules, such as PD-1, T cell immunoglobulin mucin-3, and lymphocyte-activation gene-3; furthermore, it functioned as a lymphocyte exhaustion marker. In addition, PTPN3-suppressed activated lymphocytes promoted the mammalian target of rapamycin (mTOR)-Akt signaling pathway activation and enhanced proliferation, migration, and cytotoxic activities under hypoxic conditions. Furthermore, PTPN3 suppression in activated lymphocytes increased PD-1 expression and enhanced the antitumor effects of anti-PD-1 antibody drugs against head and neck cancer in vitro and in vivo. These results suggest that the suppression of PTPN3 expression in activated lymphocytes enhances the therapeutic effect of anti-PD-1 antibody drugs in head and neck cancer, especially under hypoxic conditions that cause lymphocyte exhaustion.

在肿瘤微环境中,细胞毒性淋巴细胞与癌细胞相互作用,促进了免疫检查点抑制剂的靶点--淋巴细胞衰竭。然而,这些抑制剂的疗效有限,提高应答率仍具有挑战性。我们曾报道,蛋白酪氨酸磷酸酶非受体型(PTPN)3 是活化淋巴细胞的潜在免疫检查点分子,抑制 PTPN3 应成为癌症免疫疗法开发的重点领域。因此,在本研究中,我们从癌症微环境缺氧条件下淋巴细胞衰竭的角度出发,重点研究了PTPN3抑制疗法,并探讨了改善抗程序性死亡受体(PD)-1抗体药物反应的措施。我们发现,在缺氧条件下,活化淋巴细胞中的PTPN3表达上调,这与其他免疫检查点分子(如PD-1、T细胞免疫球蛋白粘蛋白-3和淋巴细胞活化基因-3)的研究结果相似;此外,它还具有淋巴细胞衰竭标志物的功能。此外,在缺氧条件下,PTPN3抑制的活化淋巴细胞促进了哺乳动物雷帕霉素靶标(mTOR)-Akt信号通路的活化,并增强了增殖、迁移和细胞毒性活性。此外,抑制活化淋巴细胞中的 PTPN3 可增加 PD-1 的表达,增强抗 PD-1 抗体药物在体外和体内对头颈癌的抗肿瘤作用。这些结果表明,抑制活化淋巴细胞中 PTPN3 的表达可增强抗 PD-1 抗体药物对头颈癌的治疗效果,尤其是在导致淋巴细胞衰竭的缺氧条件下。
{"title":"Inhibition of PTPN3 Expressed in Activated Lymphocytes Enhances the Antitumor Effects of Anti-PD-1 Therapy in Head and Neck Cancer, Especially in Hypoxic Environments.","authors":"Shogo Masuda, Hideya Onishi, Naoya Iwamoto, Akira Imaizumi, Satoko Koga, Shinjiro Nagao, Keita Sakanashi, Shinsaku Itoyama, Akiko Fujimura, Noritaka Komune, Ryunosuke Kogo, Masayo Umebayashi, Takashi Morisaki, Takashi Nakagawa","doi":"10.1097/CJI.0000000000000503","DOIUrl":"10.1097/CJI.0000000000000503","url":null,"abstract":"<p><p>In the tumor microenvironment, wherein cytotoxic lymphocytes interact with cancer cells, lymphocyte exhaustion, an immune checkpoint inhibitor target, is promoted. However, the efficacy of these inhibitors is limited, and improving response rates remains challenging. We previously reported that protein tyrosine phosphatase nonreceptor type (PTPN) 3 is a potential immune checkpoint molecule for activated lymphocytes and that PTPN3 inhibition should be a focus area for cancer immunotherapy development. Therefore, in this study, we focused on PTPN3-suppressive therapy in terms of lymphocyte exhaustion under hypoxic conditions, which are a cancer microenvironment, and investigated measures for improving the response to anti-programmed death receptor (PD)-1 antibody drugs. We found that PTPN3 expression was upregulated in activated lymphocytes under hypoxic conditions, similar to the findings for other immune checkpoint molecules, such as PD-1, T cell immunoglobulin mucin-3, and lymphocyte-activation gene-3; furthermore, it functioned as a lymphocyte exhaustion marker. In addition, PTPN3-suppressed activated lymphocytes promoted the mammalian target of rapamycin (mTOR)-Akt signaling pathway activation and enhanced proliferation, migration, and cytotoxic activities under hypoxic conditions. Furthermore, PTPN3 suppression in activated lymphocytes increased PD-1 expression and enhanced the antitumor effects of anti-PD-1 antibody drugs against head and neck cancer in vitro and in vivo. These results suggest that the suppression of PTPN3 expression in activated lymphocytes enhances the therapeutic effect of anti-PD-1 antibody drugs in head and neck cancer, especially under hypoxic conditions that cause lymphocyte exhaustion.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mucin-1-Targeted Chimeric Antigen Receptor T Cells Are Effective and Safe in Controlling Solid Tumors in Immunocompetent Host. 以 Mucin-1 为靶点的嵌合抗原受体 T 细胞能有效、安全地控制免疫功能正常宿主的实体瘤。
IF 3.9 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-01 Epub Date: 2024-01-25 DOI: 10.1097/CJI.0000000000000505
Ru Zhou, Shu-Ta Wu, Mahboubeh Yazdanifar, Chandra Williams, Alexa Sanders, Cory Brouwer, John Maher, Pinku Mukherjee

The chimeric antigen receptor (CAR) T-cell therapy in solid epithelial tumors has been explored, however, with limited success. As much of the preclinical work has relied on xenograft models in immunocompromised animals, the immune-related efficacies and toxicities may have been missed. In this study, we engineered syngeneic murine CAR T cells targeting the tumor form of human mucin-1 (tMUC1) and tested the MUC1 CAR T cells' efficacy and toxicity in the immunocompetent human MUC1-expressing mouse models. The MUC1 CAR T cells significantly eliminated murine pancreatic and breast cancer cell lines in vitro. In vivo, MUC1 CAR T cells significantly slowed the mammary gland tumor progression in the spontaneous PyVMT×MUC1.Tg (MMT) mice, prevented lung metastasis, and prolonged survival. Most importantly, there was minimal short or long-term toxicity with acceptable levels of transient liver toxicity but no kidney toxicity. In addition, the mice did not show any signs of weight loss or other behavioral changes with the treatment. We also report that a single dose of MUC1 CAR T-cell treatment modestly reduced the pancreatic tumor burden in a syngeneic orthotopic model of pancreatic ductal adenocarcinoma given at late stage of an established tumor. Taken together, these findings suggested the further development of tMUC1-targeted CAR T cells as an effective and relatively safe treatment modality for various tMUC1-expressing solid tumors.

对实体上皮肿瘤的嵌合抗原受体(CAR)T 细胞疗法进行了探索,但成效有限。由于大部分临床前研究都依赖于免疫受损动物的异种移植模型,因此可能会忽略与免疫相关的疗效和毒性。在这项研究中,我们设计了以肿瘤形式的人类粘蛋白-1(tMUC1)为靶点的同种异体小鼠 CAR T 细胞,并在免疫功能正常的人类 MUC1 表达小鼠模型中测试了 MUC1 CAR T 细胞的疗效和毒性。在体外,MUC1 CAR T 细胞能明显消除小鼠胰腺癌和乳腺癌细胞系。在体内,MUC1 CAR T细胞明显减缓了自发性PyVMT×MUC1.Tg(MMT)小鼠乳腺肿瘤的进展,防止了肺转移,延长了生存期。最重要的是,小鼠的短期或长期毒性极小,一过性肝脏毒性水平可接受,但肾脏无毒性。此外,小鼠在治疗过程中没有出现任何体重减轻或其他行为变化的迹象。我们还报告说,在胰腺导管腺癌成熟晚期,单剂量 MUC1 CAR T 细胞治疗可适度减轻胰腺肿瘤负荷。综上所述,这些研究结果表明,tMUC1靶向CAR T细胞是治疗各种表达tMUC1的实体瘤的一种有效且相对安全的方法。
{"title":"Mucin-1-Targeted Chimeric Antigen Receptor T Cells Are Effective and Safe in Controlling Solid Tumors in Immunocompetent Host.","authors":"Ru Zhou, Shu-Ta Wu, Mahboubeh Yazdanifar, Chandra Williams, Alexa Sanders, Cory Brouwer, John Maher, Pinku Mukherjee","doi":"10.1097/CJI.0000000000000505","DOIUrl":"10.1097/CJI.0000000000000505","url":null,"abstract":"<p><p>The chimeric antigen receptor (CAR) T-cell therapy in solid epithelial tumors has been explored, however, with limited success. As much of the preclinical work has relied on xenograft models in immunocompromised animals, the immune-related efficacies and toxicities may have been missed. In this study, we engineered syngeneic murine CAR T cells targeting the tumor form of human mucin-1 (tMUC1) and tested the MUC1 CAR T cells' efficacy and toxicity in the immunocompetent human MUC1-expressing mouse models. The MUC1 CAR T cells significantly eliminated murine pancreatic and breast cancer cell lines in vitro. In vivo, MUC1 CAR T cells significantly slowed the mammary gland tumor progression in the spontaneous PyVMT×MUC1.Tg (MMT) mice, prevented lung metastasis, and prolonged survival. Most importantly, there was minimal short or long-term toxicity with acceptable levels of transient liver toxicity but no kidney toxicity. In addition, the mice did not show any signs of weight loss or other behavioral changes with the treatment. We also report that a single dose of MUC1 CAR T-cell treatment modestly reduced the pancreatic tumor burden in a syngeneic orthotopic model of pancreatic ductal adenocarcinoma given at late stage of an established tumor. Taken together, these findings suggested the further development of tMUC1-targeted CAR T cells as an effective and relatively safe treatment modality for various tMUC1-expressing solid tumors.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pathologic Complete Response After Gastric Artery Chemoembolization Combined With Tislelizumab for Neoadjuvant Therapy of Locally Advanced Gastric Cancer: A Case Report. 胃动脉化疗栓塞联合替利单抗新辅助治疗局部晚期胃癌病理完全缓解1例
IF 3.9 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-01 Epub Date: 2023-11-23 DOI: 10.1097/CJI.0000000000000488
Yufu Lin, Yabo Chen, Shenggan Lin, Jingmei Zheng, Xiuping Zhang, Lu Gan

Gastric cancer is the most common type of gastrointestinal cancer in China which about 80% of patients are locally advanced or advanced when diagnosed. Surgery along brings high recurrence rate for locally advanced gastric cancer (LAGC), and neoadjuvant therapies are needed. The use of programmed cell death-1 (PD-1)/programmed death-ligand 1 inhibitor nowadays improved the disease-free survival for LAGC, however, only <35% of patients achieved pathologic complete response (pCR) after neoadjuvant therapy nowadays. Therefore, new regimens are needed to be investigated. Gastric artery chemoembolization is applied to metastasis gastric cancer and researches showed interventional therapy can enhance the antitumor effect of PD-1 inhibitor. Here, for the first time, we combined gastric artery chemoembolization with tislelizumab (a PD-1 inhibitor) for neoadjuvant therapy of a patient with LAGC. The patient achieved pCR after a D2 resection and tumor regression grade score was 1. After surgery, the patient received tislelizumab 200 mg per 3 weeks, and showed no sign of recurrence after 6 months of follow-up. The study indicated the use of tislelizumab and gastric artery chemoembolization for neoadjuvant therapy may bring a better pCR rate and prognosis of LAGC.

胃癌是中国最常见的胃肠道肿瘤类型,约80%的患者在确诊时为局部晚期或晚期。局部进展期胃癌(LAGC)术后复发率高,需要新辅助治疗。目前使用程序性细胞死亡-1 (PD-1)/程序性死亡配体-1抑制剂可改善LAGC的无病生存
{"title":"Pathologic Complete Response After Gastric Artery Chemoembolization Combined With Tislelizumab for Neoadjuvant Therapy of Locally Advanced Gastric Cancer: A Case Report.","authors":"Yufu Lin, Yabo Chen, Shenggan Lin, Jingmei Zheng, Xiuping Zhang, Lu Gan","doi":"10.1097/CJI.0000000000000488","DOIUrl":"10.1097/CJI.0000000000000488","url":null,"abstract":"<p><p>Gastric cancer is the most common type of gastrointestinal cancer in China which about 80% of patients are locally advanced or advanced when diagnosed. Surgery along brings high recurrence rate for locally advanced gastric cancer (LAGC), and neoadjuvant therapies are needed. The use of programmed cell death-1 (PD-1)/programmed death-ligand 1 inhibitor nowadays improved the disease-free survival for LAGC, however, only <35% of patients achieved pathologic complete response (pCR) after neoadjuvant therapy nowadays. Therefore, new regimens are needed to be investigated. Gastric artery chemoembolization is applied to metastasis gastric cancer and researches showed interventional therapy can enhance the antitumor effect of PD-1 inhibitor. Here, for the first time, we combined gastric artery chemoembolization with tislelizumab (a PD-1 inhibitor) for neoadjuvant therapy of a patient with LAGC. The patient achieved pCR after a D2 resection and tumor regression grade score was 1. After surgery, the patient received tislelizumab 200 mg per 3 weeks, and showed no sign of recurrence after 6 months of follow-up. The study indicated the use of tislelizumab and gastric artery chemoembolization for neoadjuvant therapy may bring a better pCR rate and prognosis of LAGC.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A New Method for Constructing Macrophage-Associated Predictors of Treatment Efficacy Based on Single-Cell Sequencing Analysis. 基于单细胞测序分析构建巨噬细胞相关治疗效果预测因子的新方法
IF 3.9 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-02-01 Epub Date: 2023-11-20 DOI: 10.1097/CJI.0000000000000497
Jianxiu Lin, Yang Ran, Tengfei Wu, Zishan Wang, Jinjin Zhao, Yun Tian

Tumor-associated macrophages (TAMs) are highly infiltrated in the tumor microenvironment (TME) of colorectal cancer (CRC) and play a vital role in CRC's development as well as prognosis. The required data were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas. Univariate Cox regression and least absolute shrinkage operator analyses were executed for model construction. TME assessment and immune prediction were performed using the ESTIMATE software package and the single sample genome enrichment analysis algorithm. The results show patients with low a TAMs risk score (TRS) had a better prognosis in both The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Patients with low TRS were more sensitive to 3 chemotherapeutic agents: oxaliplatin, paclitaxel, and cisplatin ( P <0.05). TME assessment showed that the low TRS group had less infiltration of M2 macrophages and regulatory T cells, but CD4 + T cells, NK cells, and dendritic cells occupy a greater proportion of TME. Low TRS group patients have a low StromalScore and ImmuneScore but have high TumorPurity. The immune checkpoint TIM-3 gene HAVCR2 expression was significantly higher in the high TRS group. Finally, we created a nomogram including TRS for forecasting survival, and TRS was significantly associated with the clinical stage of the patients. In conclusion, the TRS serves as a reliable prognostic indicator of CRC; it predicts patient outcomes to immunotherapy and chemotherapy and provides genomic evidence for the subsequent development of modulated TAMs for treating CRC.

肿瘤相关巨噬细胞(tumor -associated macrophages, tam)高度浸润于结直肠癌(CRC)的肿瘤微环境(tumor microenvironment, TME)中,在结直肠癌的发生发展和预后中起着至关重要的作用。所需数据来自基因表达综合数据库和癌症基因组图谱。单变量Cox回归和最小绝对收缩算子分析用于模型构建。采用ESTIMATE软件包和单样本基因组富集分析算法进行TME评估和免疫预测。结果显示,在The Cancer Genome Atlas和Gene Expression Omnibus队列中,TAMs风险评分(TRS)较低的患者预后较好。低TRS患者对奥沙利铂、紫杉醇和顺铂3种化疗药物更敏感(P
{"title":"A New Method for Constructing Macrophage-Associated Predictors of Treatment Efficacy Based on Single-Cell Sequencing Analysis.","authors":"Jianxiu Lin, Yang Ran, Tengfei Wu, Zishan Wang, Jinjin Zhao, Yun Tian","doi":"10.1097/CJI.0000000000000497","DOIUrl":"10.1097/CJI.0000000000000497","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) are highly infiltrated in the tumor microenvironment (TME) of colorectal cancer (CRC) and play a vital role in CRC's development as well as prognosis. The required data were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas. Univariate Cox regression and least absolute shrinkage operator analyses were executed for model construction. TME assessment and immune prediction were performed using the ESTIMATE software package and the single sample genome enrichment analysis algorithm. The results show patients with low a TAMs risk score (TRS) had a better prognosis in both The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Patients with low TRS were more sensitive to 3 chemotherapeutic agents: oxaliplatin, paclitaxel, and cisplatin ( P <0.05). TME assessment showed that the low TRS group had less infiltration of M2 macrophages and regulatory T cells, but CD4 + T cells, NK cells, and dendritic cells occupy a greater proportion of TME. Low TRS group patients have a low StromalScore and ImmuneScore but have high TumorPurity. The immune checkpoint TIM-3 gene HAVCR2 expression was significantly higher in the high TRS group. Finally, we created a nomogram including TRS for forecasting survival, and TRS was significantly associated with the clinical stage of the patients. In conclusion, the TRS serves as a reliable prognostic indicator of CRC; it predicts patient outcomes to immunotherapy and chemotherapy and provides genomic evidence for the subsequent development of modulated TAMs for treating CRC.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Core Needle Biopsies as an Alternative Source for Ex Vivo Expanded TIL for Adoptive Cell Therapy in Triple-Negative Breast Cancer. 核心针活检作为三阴性乳腺癌过继细胞治疗的体外扩展TIL的替代来源。
IF 3.9 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-02-01 Epub Date: 2023-11-22 DOI: 10.1097/CJI.0000000000000495
Magdalena M Coman, Lajos Pusztai, Regina Hooley, Liva Andreveja, Leah Kim, Nikhil Joshi, Alexey Bersenev, Diane Krause, Tristen S Park

Adoptive transfer of ex vivo expanded tumor-infiltrating lymphocytes (TILs) have produced long-term response in metastatic cancers. TILs have traditionally been expanded from surgically resected specimens. Ultrasound-guided core needle biopsy (CNB) is an alternative method that avoids the morbidity of surgery and have added benefits which may include patients not amenable to surgery as well as the potential to produce TILs from multiple lesions in the same patient. We assessed the ability to produce and expand TILs from primary triple-negative breast cancer tumors from CNB (n=7) and demonstrate comparable expansion, phenotype and cytokine secretion after phorbol myristate acetate-ionomycin stimulation to TILs expanded from surgery (n=6). T cell Receptor clonality and diversity were also comparable between the two cohorts throughout the TIL culture. CNB is a safe and feasible method to obtain tumor tissue for TIL generation in patients with triple-negative breast cancer.

体外扩增肿瘤浸润淋巴细胞(TILs)的过继转移在转移性癌症中产生了长期的反应。传统上,til是从手术切除的标本中扩展出来的。超声引导下的核心穿刺活检(CNB)是一种替代方法,它避免了手术的发病率,并有额外的好处,可能包括不适合手术的患者,以及同一患者的多个病变产生TILs的潜力。我们评估了来自CNB的原发性三阴性乳腺癌肿瘤产生和扩大TILs的能力(n=7),并证明了在肉豆酸酯-离子霉素刺激后,TILs的扩大、表型和细胞因子分泌与手术后扩大的TILs相当(n=6)。在整个TIL培养过程中,两个队列之间的T细胞受体克隆性和多样性也具有可比性。CNB是三阴性乳腺癌患者获取肿瘤组织用于TIL生成的一种安全可行的方法。
{"title":"Core Needle Biopsies as an Alternative Source for Ex Vivo Expanded TIL for Adoptive Cell Therapy in Triple-Negative Breast Cancer.","authors":"Magdalena M Coman, Lajos Pusztai, Regina Hooley, Liva Andreveja, Leah Kim, Nikhil Joshi, Alexey Bersenev, Diane Krause, Tristen S Park","doi":"10.1097/CJI.0000000000000495","DOIUrl":"10.1097/CJI.0000000000000495","url":null,"abstract":"<p><p>Adoptive transfer of ex vivo expanded tumor-infiltrating lymphocytes (TILs) have produced long-term response in metastatic cancers. TILs have traditionally been expanded from surgically resected specimens. Ultrasound-guided core needle biopsy (CNB) is an alternative method that avoids the morbidity of surgery and have added benefits which may include patients not amenable to surgery as well as the potential to produce TILs from multiple lesions in the same patient. We assessed the ability to produce and expand TILs from primary triple-negative breast cancer tumors from CNB (n=7) and demonstrate comparable expansion, phenotype and cytokine secretion after phorbol myristate acetate-ionomycin stimulation to TILs expanded from surgery (n=6). T cell Receptor clonality and diversity were also comparable between the two cohorts throughout the TIL culture. CNB is a safe and feasible method to obtain tumor tissue for TIL generation in patients with triple-negative breast cancer.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
LOXL4 Shuttled by Tumor Cells-derived Extracellular Vesicles Promotes Immune Escape in Hepatocellular Carcinoma by Activating the STAT1/PD-L1 Axis. 肿瘤细胞来源的细胞外囊泡通过激活STAT1/PD-L1轴促进肝细胞癌的免疫逃逸
IF 3.9 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-02-01 Epub Date: 2023-12-04 DOI: 10.1097/CJI.0000000000000496
Le Zhao, Ruifeng Pei, Yiren Ding, Zhan Su, Deqiang Li, Shuo Zhu, Lu Xu, Hongying Zhao, Wuyuan Zhou

Emerging evidence has validated that extracellular vesicles (EVs) regulate hepatocellular carcinoma (HCC) progression, while its role in HCC immune escape remains to be elucidated. This study investigates the role of EVs-encapsulated lysyl oxidase like-4 (LOXL4) derived from tumor cells in HCC immune escape. HCC-related microarray data sets GSE36376 and GSE87630 were obtained for differential analysis, followed by identifying the essential genes related to the prognosis of HCC patients. Bone marrow-derived macrophages were treated with EVs derived from mouse Hepa 1-6 cells and cocultured with CD8 + T cells to observe the CD8 + T-cell activity. At last, a mouse HCC orthotopic xenograft model was constructed to verify the effects of HCC cell-derived EVs on the immune escape of HCC cells and tumorigenicity in vivo by delivering LOXL4. It was found that ACAT1, C4BPA, EHHADH, and LOXL4 may be the essential genes related to the prognosis of HCC patients. On the basis of the TIMER database, there was a close correlation between LOXL4 and macrophage infiltration in HCC. Besides, STAT1 was closely related to LOXL4. In vitro experiments demonstrated that LOXL4 could induce programmed death-ligand 1 expression in macrophages and immunosuppression by activating STAT1. In vivo experiments also verified that HCC cell-derived EVs promoted the immune escape of HCC cells and tumorigenicity by delivering LOXL4. LOXL4 was delivered into macrophages via EVs to induce programmed death-ligand 1 by activating STAT1 and inhibiting the killing ability of CD8 + T cells to HCC cells, thus promoting immune escape in HCC.

新出现的证据证实,细胞外囊泡(EVs)调节肝细胞癌(HCC)的进展,但其在HCC免疫逃逸中的作用仍有待阐明。本研究探讨来自肿瘤细胞的ev包封赖氨酸氧化酶样4 (LOXL4)在HCC免疫逃逸中的作用。获取HCC相关微阵列数据集GSE36376和GSE87630进行差异分析,确定与HCC患者预后相关的必要基因。用小鼠Hepa 1-6细胞衍生的ev处理骨髓源性巨噬细胞,并与CD8+ T细胞共培养,观察CD8+ T细胞活性。最后,构建小鼠肝癌原位异种移植模型,验证肝癌细胞源性ev通过传递LOXL4对肝癌细胞免疫逃逸和体内致瘤性的影响。我们发现ACAT1、C4BPA、EHHADH、LOXL4可能是与HCC患者预后相关的重要基因。根据TIMER数据库,肝癌中LOXL4与巨噬细胞浸润密切相关。此外,STAT1与LOXL4密切相关。体外实验表明,LOXL4可通过激活STAT1诱导巨噬细胞程序性死亡配体1的表达和免疫抑制。体内实验也证实了肝细胞源性ev通过传递LOXL4促进肝细胞的免疫逃逸和致瘤性。LOXL4通过EVs进入巨噬细胞,通过激活STAT1,抑制CD8+ T细胞对HCC细胞的杀伤能力,诱导程序性死亡配体1,从而促进HCC的免疫逃逸。
{"title":"LOXL4 Shuttled by Tumor Cells-derived Extracellular Vesicles Promotes Immune Escape in Hepatocellular Carcinoma by Activating the STAT1/PD-L1 Axis.","authors":"Le Zhao, Ruifeng Pei, Yiren Ding, Zhan Su, Deqiang Li, Shuo Zhu, Lu Xu, Hongying Zhao, Wuyuan Zhou","doi":"10.1097/CJI.0000000000000496","DOIUrl":"10.1097/CJI.0000000000000496","url":null,"abstract":"<p><p>Emerging evidence has validated that extracellular vesicles (EVs) regulate hepatocellular carcinoma (HCC) progression, while its role in HCC immune escape remains to be elucidated. This study investigates the role of EVs-encapsulated lysyl oxidase like-4 (LOXL4) derived from tumor cells in HCC immune escape. HCC-related microarray data sets GSE36376 and GSE87630 were obtained for differential analysis, followed by identifying the essential genes related to the prognosis of HCC patients. Bone marrow-derived macrophages were treated with EVs derived from mouse Hepa 1-6 cells and cocultured with CD8 + T cells to observe the CD8 + T-cell activity. At last, a mouse HCC orthotopic xenograft model was constructed to verify the effects of HCC cell-derived EVs on the immune escape of HCC cells and tumorigenicity in vivo by delivering LOXL4. It was found that ACAT1, C4BPA, EHHADH, and LOXL4 may be the essential genes related to the prognosis of HCC patients. On the basis of the TIMER database, there was a close correlation between LOXL4 and macrophage infiltration in HCC. Besides, STAT1 was closely related to LOXL4. In vitro experiments demonstrated that LOXL4 could induce programmed death-ligand 1 expression in macrophages and immunosuppression by activating STAT1. In vivo experiments also verified that HCC cell-derived EVs promoted the immune escape of HCC cells and tumorigenicity by delivering LOXL4. LOXL4 was delivered into macrophages via EVs to induce programmed death-ligand 1 by activating STAT1 and inhibiting the killing ability of CD8 + T cells to HCC cells, thus promoting immune escape in HCC.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Proportion of Myeloid-derived Suppressor Cells in the Graft as a Potential Predictor of Acute Graft-versus-host Disease in Haploid Allogeneic Hematopoietic Stem Cell Transplantation. 移植物中髓源性抑制细胞的比例是单倍体异基因造血干细胞移植中急性移植物抗宿主疾病的潜在预测指标。
IF 3.9 4区 医学 Q1 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-02-01 Epub Date: 2023-12-12 DOI: 10.1097/CJI.0000000000000499
Junjie Cao, Renzhi Pei, Ying Lu, Dong Chen, Xiaohong Du, Xuhui Liu, Shuangyue Li

Myeloid-derived suppressor cells (MDSC) are powerful immunomodulatory cells that play an important role in infectious and inflammatory disorders, but the correlation between graft MDSC amount and early transplant outcomes remains unknown in allogeneic hematopoietic stem cell transplantation. We collected data from 91 patients with acute leukemia undergoing haploidentical allogeneic hematopoietic stem cell transplantation. The grafts were analyzed in terms of CD34+ cells, CD3+ T cells and subpopulation, and MDSC (HLA-DR -/low CD33 + CD16 - ) by flow cytometry. The cutoff value of the MDSC proportion in the graft on the receiver operating curve was 8.89%, with a sensitivity of 0.833 and specificity of 0.852. Day +100 cumulative incidences of II-IV and III-IV acute graft-versus-host disease (aGVHD) in the low MDSC group were 73.5% and 38.8%, respectively, and that in the high MDSC group were 5.3% and 0%, with a significant difference in incidences of II-IV and III-IV aGVHD ( P <0.001). The overall survival, relapse-free survival, and GVHD-relapse-free survival (GRFS) at 1 year were 66.3% versus 80.5% ( P =0.043), 71.6% versus 71.7% ( P =0.248), and 22.1% versus 62.8% ( P <0.001), respectively. No significant difference in the cumulative incidence of relapse between the 2 groups was observed. Multivariate analysis revealed that higher MDSC proportions were associated with a lower risk of II-IV aGVHD. Graft MDSC proportion exceeding 8.89% was significantly associated with higher overall survival and GRFS. The prophylaxis of antithymocyte globulin+post-transplant cyclophosphamide and higher MDSC proportion in the graft were favorable factors for improving GRFS. In conclusion, graft MDSC proportion may be a significant predictor of aGVHD.

髓源性抑制细胞(MDSC)是一种强大的免疫调节细胞,在感染性和炎症性疾病中发挥着重要作用,但在异体造血干细胞移植中,移植物MDSC数量与早期移植结果之间的相关性仍然未知。我们收集了91名接受单倍体异基因造血干细胞移植的急性白血病患者的数据。通过流式细胞术分析了移植物中的CD34+细胞、CD3+ T细胞和亚群以及MDSC(HLA-DR-/低CD33+CD16-)。在接收者操作曲线上,移植物中 MDSC 比例的临界值为 8.89%,灵敏度为 0.833,特异度为 0.852。第 +100 天,低 MDSC 组 II-IV 和 III-IV 急性移植物抗宿主病(aGVHD)的累积发生率分别为 73.5% 和 38.8%,而高 MDSC 组分别为 5.3% 和 0%,II-IV 和 III-IV aGVHD 的发生率差异显著(P<0.05)。
{"title":"The Proportion of Myeloid-derived Suppressor Cells in the Graft as a Potential Predictor of Acute Graft-versus-host Disease in Haploid Allogeneic Hematopoietic Stem Cell Transplantation.","authors":"Junjie Cao, Renzhi Pei, Ying Lu, Dong Chen, Xiaohong Du, Xuhui Liu, Shuangyue Li","doi":"10.1097/CJI.0000000000000499","DOIUrl":"10.1097/CJI.0000000000000499","url":null,"abstract":"<p><p>Myeloid-derived suppressor cells (MDSC) are powerful immunomodulatory cells that play an important role in infectious and inflammatory disorders, but the correlation between graft MDSC amount and early transplant outcomes remains unknown in allogeneic hematopoietic stem cell transplantation. We collected data from 91 patients with acute leukemia undergoing haploidentical allogeneic hematopoietic stem cell transplantation. The grafts were analyzed in terms of CD34+ cells, CD3+ T cells and subpopulation, and MDSC (HLA-DR -/low CD33 + CD16 - ) by flow cytometry. The cutoff value of the MDSC proportion in the graft on the receiver operating curve was 8.89%, with a sensitivity of 0.833 and specificity of 0.852. Day +100 cumulative incidences of II-IV and III-IV acute graft-versus-host disease (aGVHD) in the low MDSC group were 73.5% and 38.8%, respectively, and that in the high MDSC group were 5.3% and 0%, with a significant difference in incidences of II-IV and III-IV aGVHD ( P <0.001). The overall survival, relapse-free survival, and GVHD-relapse-free survival (GRFS) at 1 year were 66.3% versus 80.5% ( P =0.043), 71.6% versus 71.7% ( P =0.248), and 22.1% versus 62.8% ( P <0.001), respectively. No significant difference in the cumulative incidence of relapse between the 2 groups was observed. Multivariate analysis revealed that higher MDSC proportions were associated with a lower risk of II-IV aGVHD. Graft MDSC proportion exceeding 8.89% was significantly associated with higher overall survival and GRFS. The prophylaxis of antithymocyte globulin+post-transplant cyclophosphamide and higher MDSC proportion in the graft were favorable factors for improving GRFS. In conclusion, graft MDSC proportion may be a significant predictor of aGVHD.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138805484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of Immunotherapy
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1