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Neoadjuvant immune checkpoint inhibitor reduced recurrence in operable NSCLC patients with pathological complete response: a retrospective analysis. 新辅助免疫检查点抑制剂降低了病理完全应答的可手术非小细胞肺癌患者的复发率:一项回顾性分析。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-11-08 DOI: 10.1186/s12885-024-13142-4
Yanxiong Mao, Fei Chen, Zhangqun Ye, Zhouyang Li, Bo Fan, Yimin Zou, Wen Li, Fen Lan

Background: This study aimed to evaluate if neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy (CT) reduced tumor recurrence after surgery than neoadjuvant CT alone in non-small cell lung cancer (NSCLC) patients with pathologic complete response (pCR).

Methods: From January 1st 2019 to April 30th 2022, 16 NSCLC patients with pCR who received both neoadjuvant ICI and CT were designated as ICI/CT group. Another 8 patients, who received neoadjuvant CT alone, were designated as CT group. The tumor recurrence and patients' survival status were analyzed.

Results: Squamous cell carcinoma was the predominant histology type in both groups. The CT group had higher percentage of patients who received adjuvant CT than the ICI/CT group (100% vs. 75%, p = 0.046). All patients had been followed up for at least 20 months. At 20 months after surgery, the ICI/CT group had a tumor recurrence rate of 6.25%, which was significantly lower than 37.5% recurrence rate of the CT group. One patient of the CT group died of gastrointestinal hemorrhage and severe anemia at 11 months after surgery, and no patient in the ICI/CT group died. During adjuvant therapy, the ICI/CT group had significantly lower risk of anemia (12.5% vs. 50%) than the CT group (p = 0.046).

Conclusion: The study found that in NSCLC patients with pCR, neoadjuvant ICI reduced tumor recurrence rate. This indicated that like in advanced stage NSCLC, the ICI might bring similar long-term anti-tumor effect in operable NSCLC patients.

研究背景本研究旨在评估新辅助免疫检查点抑制剂(ICI)加化疗(CT)是否比单纯新辅助CT能减少病理完全反应(pCR)的非小细胞肺癌(NSCLC)患者术后肿瘤复发:从2019年1月1日至2022年4月30日,16名同时接受新辅助ICI和CT治疗的pCR非小细胞肺癌患者被指定为ICI/CT组。另外8名仅接受新辅助CT治疗的患者被定为CT组。对肿瘤复发和患者生存状况进行了分析:两组患者的组织学类型均以鳞癌为主。CT 组接受辅助 CT 的患者比例高于 ICI/CT 组(100% 对 75%,P = 0.046)。所有患者均接受了至少20个月的随访。术后20个月时,ICI/CT组的肿瘤复发率为6.25%,明显低于CT组37.5%的复发率。CT 组的一名患者在术后 11 个月因消化道出血和严重贫血死亡,而 ICI/CT 组没有患者死亡。在辅助治疗期间,ICI/CT组发生贫血的风险(12.5%对50%)明显低于CT组(P = 0.046):研究发现,对于pCR的NSCLC患者,新辅助ICI可降低肿瘤复发率。这表明,与晚期NSCLC患者一样,ICI也可能为可手术的NSCLC患者带来类似的长期抗肿瘤效果。
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引用次数: 0
Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide. 基于Ki67指数和免疫微环境的转移性胰腺神经内分泌肿瘤对卡培他滨加替莫唑胺治疗的分级。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-11-07 DOI: 10.1186/s12885-024-13117-5
Heli Gao, Wuhu Zhang, Zheng Li, Wensheng Liu, Mengqi Liu, Qifeng Zhuo, Yihua Shi, Wenyan Xu, Chenjie Zhou, Yi Qin, Jin Xu, Jie Chen, Xianjun Yu, Xiaowu Xu, Shunrong Ji

Background: Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem).

Method: Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence.

Results: In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p < 0.001).

Conclusion: Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem.

背景:Ki67指数在转移性胰腺神经内分泌肿瘤(PanNET)治疗过程中会发生变化。该研究旨在检测对卡培他滨/替莫唑胺(CapTem)有反应的PanNET中基于Ki67指数和免疫微环境的分级变化:方法:收集PanNET患者的回顾性数据。在对照组中,35 名患者在活检后立即接受了手术。CapTem组中,38名患者在活检后接受了CapTem治疗,并对治疗反应良好(定义为病情稳定或部分反应),随后接受了手术。所有患者在活检和手术后都有病理 Ki67 指数。采用多重免疫荧光对CD163 + CD68 + CD206 + M2巨噬细胞、CD68 + CD86 + CD80 + M1巨噬细胞、CD11b + CD33 +髓源性抑制细胞和CD4 + CD25 +调节性T细胞进行染色:在对照组中,术后根据Ki67指数直接得出的配对分级与活检结果相比没有升级或降级。在对 CapTem 反应良好的患者中,CapTem 前后基于 Ki67 指数的分级发生了变化。13名患者的Ki67指数升高,11名患者的Ki67指数降低。升级组与降级组相比,病情稳定的比例更高(P = 0.0155)。升级组患者的 mPFS 明显短于降级组患者(8.5 个月 vs. 20 个月,HR 4.834,95% CI 1.414 至 16.53,p = 0.012)。降级组的 M1 巨噬细胞明显低于 Ki67 升级组(P 结论:降级组的 M1 巨噬细胞明显低于 Ki67 升级组):基于 Ki67 指数和免疫环境的分级在对 CapTem 反应良好的 PanNET 患者中发生了变化。降级患者的 mPFS 比升级患者更长。即使对 CapTem 反应良好的患者,也有必要在 CapTem 治疗后重新评估 Ki67 指数。
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引用次数: 0
Accurate prediction of the lymph node status in ampullary duodenal carcinoma: potential guidance for clinical management. 准确预测胰十二指肠癌的淋巴结状态:为临床治疗提供潜在指导。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-11-07 DOI: 10.1186/s12885-024-13119-3
Ran Ni, Tianpeng Zhang, Yixuan Mou, Zhiming Hu, Zongting Gu

Purpose: This study aimed to identify the risk factors associated with ampullary duodenal carcinoma (a-DC) and develop a clinical model to dynamically and accurately predict the risk of lymph node metastasis (LNM) in a-DC patients.

Methods: Data from 4077 patients (2004-2020) were extracted from the Surveillance, Epidemiology, and End Results database to form a training cohort, while 173 cases (2010-2020) from Zhejiang Provincial People's Hospital in China were used as an external validation cohort. A reliable LASSO-logistic method was employed to identify independent risk factors for a-DC LNM, and a nomogram was developed based on these factors to assess the risk of a-DC LNM. The nomogram was evaluated using the Akaike information criterion, misclassification error, area under the curve, and likelihood ratio test. Finally, the nomogram's accuracy and generalizability were externally validated..

Results: After screening using LASSO and logistic regression four variables were identified as independent risk factors for a-DC LNM: sex (P < 0.001), tumor size (P < 0.001), grade (P < 0.001), and tumor extension (P < 0.001). The area under the curve of the nomogram was 74.8% in the training group and 88.9% in the external validation group. The calibration curves demonstrated that the LNM predictions made by the nomogram were in satisfactory agreement with the actual observed LNM. Additionally, the decision curve analysis curves indicated effective clinical utility of the nomogram.

Conclusions: A nomogram based on the LASSO-logistic analysis was constructed to predict a-DC LNM, demonstrating good performance and clinical application value.

目的:本研究旨在确定与十二指肠咽癌(a-DC)相关的风险因素,并建立一个临床模型,以动态、准确地预测十二指肠咽癌患者淋巴结转移(LNM)的风险:从监测、流行病学和终末结果数据库中提取4077例患者(2004-2020年)的数据组成训练队列,同时将中国浙江省人民医院的173例患者(2010-2020年)作为外部验证队列。研究人员采用可靠的LASSO-logistic方法确定了a-DC LNM的独立风险因素,并根据这些因素绘制了评估a-DC LNM风险的提名图。使用阿凯克信息准则、误分类误差、曲线下面积和似然比检验对提名图进行了评估。最后,对提名图的准确性和可推广性进行了外部验证:在使用 LASSO 和逻辑回归进行筛选后,四个变量被确定为 a-DC LNM 的独立风险因素:性别(P 结论)、年龄(P 结论)、性别(P 结论)和年龄(P 结论):基于 LASSO 逻辑分析构建的提名图用于预测 a-DC LNM,显示出良好的性能和临床应用价值。
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引用次数: 0
Retraction Note: Lactate dehydrogenase D serves as a novel biomarker for prognosis and immune infiltration in lung adenocarcinoma. 撤稿说明:乳酸脱氢酶D是肺腺癌预后和免疫浸润的新型生物标志物。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-11-07 DOI: 10.1186/s12885-024-13137-1
Yu Zhang, Tianyi Zhang, Yingdong Zhao, Hongdi Wu, Qiang Zhen, Suwei Zhu, Shaoshuai Hou
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引用次数: 0
Interim analysis of robot-assisted radical hysterectomy in Japan: a multicenter, prospective interventional single-arm clinical trial. 日本机器人辅助根治性子宫切除术中期分析:一项多中心、前瞻性介入单臂临床试验。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-11-07 DOI: 10.1186/s12885-024-13090-z
Hiroe Ito, Yoshihito Yokoyama, Satoru Kyo, Masaki Mandai, Kenzo Kosaka, Hiroaki Kobayashi, Etsuko Miyagi, Mamiko Onuki, Koji Matsumoto, Noriomi Matsumura, Kota Umemura, Hideki Ishikawa, Keiichi Isaka

Objective: To investigate the efficacy and safety of robot-assisted radical hysterectomy (RARH) as a minimally invasive procedure in patients with cervical cancer that is curable by surgery.

Materials and methods: This study was a multicenter, open-label, single-arm clinical trial. The short-term outcome of open radical hysterectomy was used as the historical control. The primary endpoint was successful surgery with minimal blood loss (300 mL or less) and negative surgical margins. Secondary endpoints included surgical outcomes, recurrence-free survival (RFS), and overall survival (OS) rates.

Results: Overall, 101 cases were enrolled in this study at 10 participating medical institutions and 100 underwent RARH. Among these cases, 89 met the primary endpoint, exceeding the threshold of 0.75 set by the lower limit. At 2 years postoperatively, 17 cases had recurrences, 4 were classified as International federation of Obstetrics and Gynecology Stage IB1 or lower, while 13 as IB2 or higher. There were three deaths, including one in Stage IB1 and two in Stage IIB in the second postoperative year, all of which had lymph node metastasis. The oncological outcomes for all cases showed RFS and OS rates of 82.7% and 96.9%, respectively, over a median observation period of 37 months. For cases with Stage IB1, RFS and OS were 94.1% and 98.5%, respectively.

Conclusion: RARH demonstrated a significant reduction in blood loss while ensuring radicality, indicating the safety and efficacy of this procedure compared to conventional RH. Although it is conceivable that the results of this oncological analysis could change, as the data collection has not been fully completed, we plan to further evaluate the oncologic outcomes of RARH in future studies.

Trial registration: UMIN-CTR: UMIN000022278, registered on 11th May 2016.

目的研究机器人辅助根治性子宫切除术(RARH)作为一种微创手术对可通过手术治愈的宫颈癌患者的有效性和安全性:本研究是一项多中心、开放标签、单臂临床试验。以开腹根治性子宫切除术的短期疗效作为历史对照。主要终点是手术成功,失血量最少(300 毫升或更少),手术边缘阴性。次要终点包括手术结果、无复发生存率(RFS)和总生存率(OS):10家参与研究的医疗机构共招募了101例病例,其中100例接受了RARH手术。在这些病例中,89 例达到了主要终点,超过了下限设定的阈值 0.75。术后 2 年,17 例复发,4 例被归类为国际妇产科联盟 IB1 期或更低,13 例被归类为 IB2 期或更高。术后第二年有3例死亡,其中1例为IB1期,2例为IIB期,均为淋巴结转移。所有病例的肿瘤治疗结果显示,在37个月的中位观察期内,RFS和OS率分别为82.7%和96.9%。IB1期病例的RFS和OS分别为94.1%和98.5%:结论:RARH在确保根治性的同时显著减少了失血量,表明该手术与传统RH相比具有安全性和有效性。尽管由于数据收集尚未完全完成,本次肿瘤学分析的结果可能会发生变化,但我们计划在未来的研究中进一步评估 RARH 的肿瘤学结果:UMIN-CTR:UMIN000022278,注册日期:2016年5月11日。
{"title":"Interim analysis of robot-assisted radical hysterectomy in Japan: a multicenter, prospective interventional single-arm clinical trial.","authors":"Hiroe Ito, Yoshihito Yokoyama, Satoru Kyo, Masaki Mandai, Kenzo Kosaka, Hiroaki Kobayashi, Etsuko Miyagi, Mamiko Onuki, Koji Matsumoto, Noriomi Matsumura, Kota Umemura, Hideki Ishikawa, Keiichi Isaka","doi":"10.1186/s12885-024-13090-z","DOIUrl":"10.1186/s12885-024-13090-z","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the efficacy and safety of robot-assisted radical hysterectomy (RARH) as a minimally invasive procedure in patients with cervical cancer that is curable by surgery.</p><p><strong>Materials and methods: </strong>This study was a multicenter, open-label, single-arm clinical trial. The short-term outcome of open radical hysterectomy was used as the historical control. The primary endpoint was successful surgery with minimal blood loss (300 mL or less) and negative surgical margins. Secondary endpoints included surgical outcomes, recurrence-free survival (RFS), and overall survival (OS) rates.</p><p><strong>Results: </strong>Overall, 101 cases were enrolled in this study at 10 participating medical institutions and 100 underwent RARH. Among these cases, 89 met the primary endpoint, exceeding the threshold of 0.75 set by the lower limit. At 2 years postoperatively, 17 cases had recurrences, 4 were classified as International federation of Obstetrics and Gynecology Stage IB1 or lower, while 13 as IB2 or higher. There were three deaths, including one in Stage IB1 and two in Stage IIB in the second postoperative year, all of which had lymph node metastasis. The oncological outcomes for all cases showed RFS and OS rates of 82.7% and 96.9%, respectively, over a median observation period of 37 months. For cases with Stage IB1, RFS and OS were 94.1% and 98.5%, respectively.</p><p><strong>Conclusion: </strong>RARH demonstrated a significant reduction in blood loss while ensuring radicality, indicating the safety and efficacy of this procedure compared to conventional RH. Although it is conceivable that the results of this oncological analysis could change, as the data collection has not been fully completed, we plan to further evaluate the oncologic outcomes of RARH in future studies.</p><p><strong>Trial registration: </strong>UMIN-CTR: UMIN000022278, registered on 11th May 2016.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1360"},"PeriodicalIF":3.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
An in vitro investigation into the cytotoxic impact of antigen-presenting dendritic cell-tumor infiltrating lymphocytes on ovarian cancer cells. 抗原递呈树突状细胞-肿瘤浸润淋巴细胞对卵巢癌细胞细胞毒性影响的体外研究。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-11-07 DOI: 10.1186/s12885-024-13131-7
Shengnan Yang, Junrong Wang, Zhenwu Du, Chunhua Sheng, Qianyu Liu, Xuewei Lao, Donghui Xu, Ying Pan

Objective: The objective of this study is to develop a novel therapeutic approach for the treatment of ovarian cancer while investigating the role of tumor-infiltrating lymphocytes (TILs) in the context of ovarian cancer therapy. The primary aim is to establish a technical procedure for the isolation of tumor cells, lymphocytes, and dendritic cells (DCs) derived from ovarian cancer tissues or ascites. Subsequently, the focus lies on the generation of dendritic cell-tumor infiltrating lymphocytes (DC-TILs) exhibiting specific cytotoxic capabilities aimed at targeted therapeutic interventions. The cytotoxic impact of DC-TIL interactions on tumor cells was investigated through in vitro experimentation. This research aims to provide fundamental experimental insights for the future clinical advancement of TIL therapy in ovarian cancer.

Methods: The experimental samples included fresh surgical specimens and ascites specimens procured from three patients (ranging in age from 32 to 75), sourced from the Department of Gynecology at the Third Bethune Hospital of Jilin University. TILs were extracted through in vitro isolation from solid tumor tissues, while primary tumor cells and DCs were obtained from ascites specimens. Tumor-specific antigens derived from patient tumor cells were utilized to stimulate the maturation of DCs. TILs were subsequently co-cultured with antigen-stimulated DC cells. Subsequently, TILs with specific killing effects were obtained, and the cytotoxic impact of DC-TILs on tumor cells was detected in vitro.

Results: (1) TILs were successfully obtained through expansion from the tumor tissue of a patient diagnosed with ovarian cancer. (2) DCs were successfully induced from ascites cells harvested from patients diagnosed with ovarian cancer. (3) TILs significantly enhanced the cytotoxicity of tumor cells following DC stimulation.

Conclusion: TILs have the capacity to augment the cytotoxicity directed towards tumor cells following DC stimulation.

研究目的本研究的目的是开发一种治疗卵巢癌的新方法,同时研究肿瘤浸润淋巴细胞(TILs)在卵巢癌治疗中的作用。研究的主要目的是建立从卵巢癌组织或腹水中分离肿瘤细胞、淋巴细胞和树突状细胞(DCs)的技术程序。随后,重点是生成树突状细胞-肿瘤浸润淋巴细胞(DC-TILs),这些细胞具有特定的细胞毒性能力,目的是进行靶向治疗干预。通过体外实验研究了 DC-TIL 相互作用对肿瘤细胞的细胞毒性影响。这项研究旨在为未来卵巢癌 TIL 治疗的临床进展提供基础实验见解:实验样本包括来自吉林大学白求恩第三医院妇科的三名患者(年龄在 32 岁至 75 岁之间)的新鲜手术标本和腹水标本。TIL是从实体瘤组织中通过体外分离提取的,而原代肿瘤细胞和DC则是从腹水标本中获得的。从患者肿瘤细胞中提取的肿瘤特异性抗原被用来刺激DCs的成熟。随后,TIL 与抗原刺激的 DC 细胞共同培养。结果:(1)成功地从一名卵巢癌患者的肿瘤组织中扩增获得了 TILs。(2)从卵巢癌患者腹水细胞中成功诱导出 DC。(3) TILs 能显著增强 DC 刺激后肿瘤细胞的细胞毒性:结论:TILs 有能力增强 DC 刺激后针对肿瘤细胞的细胞毒性。
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引用次数: 0
Targeting LLT1 as a potential immunotherapy option for cancer patients non-responsive to existing checkpoint therapies in multiple solid tumors. 以 LLT1 为靶点,为对现有检查点疗法无反应的多种实体瘤癌症患者提供一种潜在的免疫疗法。
IF 4.3 2区 医学 Q2 ONCOLOGY Pub Date : 2024-11-07 DOI: 10.1186/s12885-024-13074-z
Tirtha Mandal, Soorya Gnanasegaran, Golding Rodrigues, Shalini Kashipathi, Anurag Tiwari, Ashvini Kumar Dubey, Sanghamitra Bhattacharjee, Yogendra Manjunath, Subith Krishna, M S Madhusudhan, Maloy Ghosh

Background: High levels of LLT1 expression have been found in several cancers, where it interacts with CD161 on NK cells to facilitate tumor immune escape. Targeting LLT1 could potentially relieve this inhibitory signal and enhance anti-tumor responses mediated through NK cells. Using the 'The Cancer Genome Atlas' (TCGA) database, we investigated the role of LLT1 in the tumor microenvironment (TME) across various cancers. Identifying such biomarkers could create new therapeutic options for patients in addition to complementing existing immunotherapies.

Methods: LLT1 expression was evaluated in 33 cancers using TCGA transcriptome data. Univariate Cox regression analysis was employed to assess the correlation of LLT1 expression with patient survival. The relationship between LLT1 expression with immune infiltrates, immune gene signatures, and cancer genomic biomarkers (TMB, MSI, and MMR) was also investigated. Immunofluorescence studies were conducted to validate LLT1 expression in tumors. Furthermore, using the CRI iAtlas data, we evaluated LLT1 distribution and its correlation with other immune checkpoint genes in patients non-responsive to existing immune checkpoint therapies across multiple solid cancers.

Results: High expression of LLT1 was observed in 12 cancers, including BRCA, CHOL, ESCA, GBM, HNSC, KIRC, KIRP, LIHC, LUAD, STAD, SARC, and PCPG. In certain cancers like COAD, KICH, and KIRC, high LLT1 expression was associated with poor prognosis. Further analysis revealed that upregulated LLT1 was associated with an abundance of NK and T cell infiltrates in the TME, as well as exhaustive immune biomarkers, and inversely associated with pro-inflammatory and tumor suppressor signatures. High LLT1 expression is also positively correlated with genomic biomarkers in certain cancers. Immunofluorescence studies confirmed moderate to high LLT1 expression in immune-resistant prostate cancer, glioma, ovarian cancer, and immune-sensitive liver cancer cell lines. An independent assessment of clinical cohorts from CRI iAtlas showed a correlation of upregulated LLT1 with multiple immunosuppressive genes in patients non-responsive to current ICIs.

Conclusions: The biomarker analysis revealed a clear association between elevated LLT1 expression and an immunosuppressive TME in patient cohorts from TCGA and clinical databases. Therefore, this study provides a foundation for utilizing LLT1 as a potential target to improve clinical responses in ICI non-responsive patients with upregulated LLT1.

背景:在几种癌症中发现了高水平的 LLT1 表达,它与 NK 细胞上的 CD161 相互作用,促进肿瘤免疫逃逸。靶向 LLT1 有可能缓解这种抑制信号,增强通过 NK 细胞介导的抗肿瘤反应。利用 "癌症基因组图谱"(TCGA)数据库,我们研究了 LLT1 在各种癌症的肿瘤微环境(TME)中的作用。除了补充现有的免疫疗法外,确定此类生物标志物还能为患者创造新的治疗选择:方法:利用 TCGA 转录组数据评估了 33 种癌症中 LLT1 的表达情况。方法:利用TCGA转录组数据评估了33种癌症中LLT1的表达情况,并采用单变量Cox回归分析评估了LLT1表达与患者生存的相关性。研究还调查了LLT1表达与免疫浸润、免疫基因特征和癌症基因组生物标志物(TMB、MSI和MMR)之间的关系。免疫荧光研究验证了 LLT1 在肿瘤中的表达。此外,我们还利用 CRI iAtlas 数据评估了 LLT1 在对现有免疫检查点疗法无反应的多种实体瘤患者中的分布情况及其与其他免疫检查点基因的相关性:结果:在 12 种癌症中观察到 LLT1 高表达,包括 BRCA、CHOL、ESCA、GBM、HNSC、KIRC、KIRP、LIHC、LUAD、STAD、SARC 和 PCPG。在某些癌症中,如 COAD、KICH 和 KIRC,LLT1 的高表达与预后不良有关。进一步的分析表明,LLT1的上调与TME中大量的NK和T细胞浸润以及详尽的免疫生物标志物有关,而与促炎和肿瘤抑制特征成反比。LLT1 的高表达还与某些癌症的基因组生物标志物呈正相关。免疫荧光研究证实,在免疫抵抗性前列腺癌、胶质瘤、卵巢癌和免疫敏感性肝癌细胞系中,LLT1 有中度到高度表达。对 CRI iAtlas 临床队列的独立评估显示,在对当前 ICIs 无反应的患者中,上调的 LLT1 与多个免疫抑制基因相关:生物标志物分析表明,在来自TCGA和临床数据库的患者队列中,LLT1表达升高与免疫抑制性TME之间存在明显关联。因此,这项研究为利用 LLT1 作为潜在靶点,改善 LLT1 上调的 ICI 无反应患者的临床反应奠定了基础。
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引用次数: 0
Efficacy and safety of PD-1/PD-L1 inhibitors in patients with Merkel Cell Carcinoma: a systematic review and Meta-analysis. PD-1/PD-L1抑制剂对梅克尔细胞癌患者的疗效和安全性:系统综述和元分析。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-11-06 DOI: 10.1186/s12885-024-13129-1
Francisco Cezar Aquino de Moraes, Michele Kreuz, Isabella Christina Amaral de Lara, Artur de Oliveira Macena Lôbo, Rommel Mario Rodríguez Burbano

Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer characterized by high rates of metastasis. Emerging evidence suggests that PD-L1/PD1 blockade holds promise as a therapeutic option for MCC. However, the efficacy and safety of this approach in treating MCC remain incompletely understood. This systematic review and meta-analysis aims to analyze the efficacy and safety of PD-1/PD-L1 blockade for patients with MCC.

Methods: PubMed, Cochrane, and Embase were searched for studies evaluating patients with MCC undergoing PD-1/PD-L1 treatment. The estimated outcomes were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). We performed the meta-analysis using RStudio v4.4.2 software.

Results: A total of 14 reports of 13 different studies encompassing 615 patients were included. The median age ranged from 64 to 77 years. Median follow-up ranged from 7.9 months to 59.3 months. Pooled OS rates at 24 and 36 months were 65.05% (95% CI 44.04-81.49) and 59.58% (95% CI 39.62-76.81), respectively, while pooled PFS rates at 6, 12, and 36 months were 51.78% (95% CI 37.83-65.45), 46.12% (95% CI 29.44-63.72), and 28.73% (95% CI 16.57-45.02), in the same order. DCR proportion was 61.65% (95% CI 54.85-68.03) and ORR was 53.79% (95% CI 47.80-59.68). The frequency of TRAEs of any grade was 61.72% (95% CI 45.75-75.51) and for TRAEs of grade ≥ 3 was 17.60% (95% CI 12.28 to 24.57).

Conclusions: This systematic review and meta-analysis revealed that patients with MCC undergoing treatment with PD-1/PDL-1 showed durable responses with continuous and clinically meaningful survival outcomes.

背景:梅克尔细胞癌(MCC)是一种罕见的侵袭性神经内分泌皮肤癌,其特点是转移率高。新的证据表明,PD-L1/PD1阻断疗法有望成为治疗梅克尔细胞癌的一种选择。然而,人们对这种方法治疗 MCC 的有效性和安全性仍不甚了解。本系统综述和荟萃分析旨在分析PD-1/PD-L1阻断治疗MCC患者的有效性和安全性:方法:检索了PubMed、Cochrane和Embase上对接受PD-1/PD-L1治疗的MCC患者进行评估的研究。估计结果包括总反应率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)、总生存期(OS)和治疗相关不良事件(TRAEs)。我们使用 RStudio v4.4.2 软件进行了荟萃分析:结果:共纳入了 13 项不同研究的 14 篇报告,涉及 615 名患者。中位年龄从 64 岁到 77 岁不等。中位随访时间从 7.9 个月到 59.3 个月不等。24个月和36个月的汇总OS率分别为65.05%(95% CI 44.04-81.49)和59.58%(95% CI 39.62-76.81),6个月、12个月和36个月的汇总PFS率依次为51.78%(95% CI 37.83-65.45)、46.12%(95% CI 29.44-63.72)和28.73%(95% CI 16.57-45.02)。DCR比例为61.65%(95% CI 54.85-68.03),ORR为53.79%(95% CI 47.80-59.68)。任何等级的TRAEs发生率为61.72%(95% CI 45.75-75.51),等级≥3的TRAEs发生率为17.60%(95% CI 12.28-24.57):这项系统综述和荟萃分析显示,接受PD-1/PDL-1治疗的MCC患者表现出持久的应答,并获得持续且有临床意义的生存结果。
{"title":"Efficacy and safety of PD-1/PD-L1 inhibitors in patients with Merkel Cell Carcinoma: a systematic review and Meta-analysis.","authors":"Francisco Cezar Aquino de Moraes, Michele Kreuz, Isabella Christina Amaral de Lara, Artur de Oliveira Macena Lôbo, Rommel Mario Rodríguez Burbano","doi":"10.1186/s12885-024-13129-1","DOIUrl":"10.1186/s12885-024-13129-1","url":null,"abstract":"<p><strong>Background: </strong>Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer characterized by high rates of metastasis. Emerging evidence suggests that PD-L1/PD1 blockade holds promise as a therapeutic option for MCC. However, the efficacy and safety of this approach in treating MCC remain incompletely understood. This systematic review and meta-analysis aims to analyze the efficacy and safety of PD-1/PD-L1 blockade for patients with MCC.</p><p><strong>Methods: </strong>PubMed, Cochrane, and Embase were searched for studies evaluating patients with MCC undergoing PD-1/PD-L1 treatment. The estimated outcomes were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). We performed the meta-analysis using RStudio v4.4.2 software.</p><p><strong>Results: </strong>A total of 14 reports of 13 different studies encompassing 615 patients were included. The median age ranged from 64 to 77 years. Median follow-up ranged from 7.9 months to 59.3 months. Pooled OS rates at 24 and 36 months were 65.05% (95% CI 44.04-81.49) and 59.58% (95% CI 39.62-76.81), respectively, while pooled PFS rates at 6, 12, and 36 months were 51.78% (95% CI 37.83-65.45), 46.12% (95% CI 29.44-63.72), and 28.73% (95% CI 16.57-45.02), in the same order. DCR proportion was 61.65% (95% CI 54.85-68.03) and ORR was 53.79% (95% CI 47.80-59.68). The frequency of TRAEs of any grade was 61.72% (95% CI 45.75-75.51) and for TRAEs of grade ≥ 3 was 17.60% (95% CI 12.28 to 24.57).</p><p><strong>Conclusions: </strong>This systematic review and meta-analysis revealed that patients with MCC undergoing treatment with PD-1/PDL-1 showed durable responses with continuous and clinically meaningful survival outcomes.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1357"},"PeriodicalIF":3.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Assessing the impact of cervical cancer education in two high schools in Ghana. 评估宫颈癌教育对加纳两所高中的影响。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-11-06 DOI: 10.1186/s12885-024-13134-4
Florence Dedey, Josephine Nsaful, Edmund Nartey, Juliana Labi, Nii Armah Adu-Aryee, Christine Kuti, Joe-Nat Clegg-Lamptey

Background: Cervical cancer is one of the commonest female cancers in Ghana. However, it is preventable. Prevention through Human Papilloma Virus immunization and early detection by screening have their foundation in awareness and a good knowledge about the disease. Acquiring the right knowledge about cervical cancer should be earlier rather than later while mindsets are still being formed to translate into the right attitudes and behaviours later in life.

Methodology: An unpaired pre- and post-test quasi experimental study was conducted at two Ghanaian senior high schools. An educational intervention was carried out comprising a drama, PowerPoint lecture, question and answer session and cervical cancer information leaflet distribution. A self-administered questionnaire was given as a pre-test and repeated as a post-test after 3 months. The total score for each domain of knowledge tested was categorized into adequate knowledge (≥ 50%) and inadequate knowledge (< 50%).

Results: The number of participants in the pre- and post-test were 1,107 and 1,276 girls respectively, with average age of 16 years. General knowledge on cervical cancer improved to 94.4% from 73% following the intervention, but only 46.2% said cervical cancer was curable following the education. Knowledge on symptoms improved from 78 to 87.1% and risk factor knowledge improved from 81.8 to 89.3%. After the intervention, 37% from an initial 42% still thought that having sex at a young age (adolescence) was not a risk factor. Screening and prevention knowledge improved from 82.9 to 91% but only 37.2% knew the recommended age to begin screening with pap smears, even after the education. Overall knowledge on cervical cancer after the education significantly improved from 79.1 to 92.3%.

Conclusion: Knowledge of cervical cancer among young girls in two High Schools, improved with the educational intervention. Areas of education to be emphasized are: cervical cancer is curable if diagnosed early, increased risk with early onset of sexual activity, and recommended age to start screening. Educating young girls on cervical cancer increases their awareness and gives them adequate knowledge which should influence their attitudes and behaviour towards cervical cancer in the future. It should be considered for adoption into high school curricula.

背景:宫颈癌是加纳最常见的女性癌症之一:宫颈癌是加纳最常见的女性癌症之一。然而,宫颈癌是可以预防的。通过人乳头瘤病毒免疫接种和筛查早期发现来预防,其基础是对该疾病的认识和良好知识。正确了解宫颈癌知识的时机应早而不是晚,因为人们的观念仍在形成之中,并将转化为日后生活中的正确态度和行为:在加纳的两所高中开展了一项无配对前后测试的准实验研究。教育干预包括戏剧表演、PowerPoint 讲座、问答环节和宫颈癌宣传单的分发。自填问卷作为前测,3 个月后重复作为后测。每个测试知识领域的总分被分为充分了解(≥ 50%)和不充分了解(结果:参加前测和后测的女孩人数分别为 1 107 人和 1 276 人,平均年龄为 16 岁。干预后,宫颈癌常识知晓率从 73%提高到 94.4%,但只有 46.2%的人在教育后表示宫颈癌是可以治愈的。对症状的了解从 78% 提高到 87.1%,对风险因素的了解从 81.8% 提高到 89.3%。干预后,37%的人仍然认为年轻时(青春期)发生性行为不是风险因素,而最初的这一比例为 42%。筛查和预防知识从 82.9%提高到 91%,但只有 37.2%的人知道开始进行子宫颈抹片筛查的建议年龄,即使在教育之后也是如此。接受教育后,宫颈癌的总体知识水平从 79.1% 显著提高到 92.3%:结论:通过教育干预,两所高中女生对宫颈癌的认识有所提高。需要强调的教育领域包括:宫颈癌如果及早诊断是可以治愈的、过早开始性活动会增加患病风险,以及建议开始筛查的年龄。对少女进行宫颈癌教育,可以提高她们对宫颈癌的认识,使她们获得足够的知识,从而影响她们今后对宫颈癌的态度和行为。应考虑将其纳入高中课程。
{"title":"Assessing the impact of cervical cancer education in two high schools in Ghana.","authors":"Florence Dedey, Josephine Nsaful, Edmund Nartey, Juliana Labi, Nii Armah Adu-Aryee, Christine Kuti, Joe-Nat Clegg-Lamptey","doi":"10.1186/s12885-024-13134-4","DOIUrl":"10.1186/s12885-024-13134-4","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer is one of the commonest female cancers in Ghana. However, it is preventable. Prevention through Human Papilloma Virus immunization and early detection by screening have their foundation in awareness and a good knowledge about the disease. Acquiring the right knowledge about cervical cancer should be earlier rather than later while mindsets are still being formed to translate into the right attitudes and behaviours later in life.</p><p><strong>Methodology: </strong>An unpaired pre- and post-test quasi experimental study was conducted at two Ghanaian senior high schools. An educational intervention was carried out comprising a drama, PowerPoint lecture, question and answer session and cervical cancer information leaflet distribution. A self-administered questionnaire was given as a pre-test and repeated as a post-test after 3 months. The total score for each domain of knowledge tested was categorized into adequate knowledge (≥ 50%) and inadequate knowledge (< 50%).</p><p><strong>Results: </strong>The number of participants in the pre- and post-test were 1,107 and 1,276 girls respectively, with average age of 16 years. General knowledge on cervical cancer improved to 94.4% from 73% following the intervention, but only 46.2% said cervical cancer was curable following the education. Knowledge on symptoms improved from 78 to 87.1% and risk factor knowledge improved from 81.8 to 89.3%. After the intervention, 37% from an initial 42% still thought that having sex at a young age (adolescence) was not a risk factor. Screening and prevention knowledge improved from 82.9 to 91% but only 37.2% knew the recommended age to begin screening with pap smears, even after the education. Overall knowledge on cervical cancer after the education significantly improved from 79.1 to 92.3%.</p><p><strong>Conclusion: </strong>Knowledge of cervical cancer among young girls in two High Schools, improved with the educational intervention. Areas of education to be emphasized are: cervical cancer is curable if diagnosed early, increased risk with early onset of sexual activity, and recommended age to start screening. Educating young girls on cervical cancer increases their awareness and gives them adequate knowledge which should influence their attitudes and behaviour towards cervical cancer in the future. It should be considered for adoption into high school curricula.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1359"},"PeriodicalIF":3.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Mesenchymal stem cell-derived exosomes carrying miR-486-5p inhibit glycolysis and cell stemness in colorectal cancer by targeting NEK2. 间充质干细胞衍生的外泌体携带miR-486-5p,通过靶向NEK2抑制结直肠癌中的糖酵解和细胞干性。
IF 3.4 2区 医学 Q2 ONCOLOGY Pub Date : 2024-11-06 DOI: 10.1186/s12885-024-13086-9
Facai Cui, Yu Chen, Xiaoyu Wu, Weifeng Zhao

Colorectal cancer (CRC) is a major global concern. Mesenchymal stem cell-derived exosomes (MSC-EXOs) have demonstrated efficacy as a therapeutic approach for colorectal cancer. However, the precise mechanism by which MSC-EXOs treat colorectal cancer remains unclear. Human umbilical cord (hUC)-MSC-EXOs were isolated and identified. Cell Counting Kit-8 (CCK-8), Transwell, and colony formation assays were used to assess the activity of CRC cells. Glucose consumption, lactic acid production, and extracellular acidification rate (ECAR) were measured to assess glycolytic activity. Cell stemness was assessed using a sphere-formation assay. Furthermore, MSC-exosomal microRNAs (miRNAs) in CRC tissues were analyzed using the EVmiRNA database, and aberrantly expressed miRNAs in CRC cells were obtained from the Gene Expression Omnibus (GEO) database. The binding relationship between miR-486-5p and the never in mitosis gene A-related kinase 2 (NEK2) was predicted using the Starbase database and validated through RNA binding protein immunoprecipitation (RIP) and dual luciferase assays. These results showed that hUC-MSC-EXOs inhibited the proliferation and metastasis of CRC cells. Moreover, glycolysis and stemness abilities of CRC cells also decreased after treatment with hUC-MSC-EXOs. miR-486-5p was found to be enriched in hUC-MSC-EXOs and significantly downregulated in CRC cells. miR-486-5p directly bound to NEK2. Overexpression of NEK2 reversed the inhibitory effect of miR-486-5p on CRC cell glycolysis and stemness. Our study highlights that hUC-MSC-EXO miR-486-5p inhibits glycolysis and cell stemness in CRC by targeting NEK2. This finding offers compelling evidence supporting the potential application of hUC-MSC-EXOs in the treatment of CRC.

结直肠癌(CRC)是全球关注的一大问题。间充质干细胞衍生外泌体(MSC-EXOs)作为一种结直肠癌治疗方法已被证明具有疗效。然而,间充质干细胞外泌体治疗结直肠癌的确切机制仍不清楚。我们分离并鉴定了人脐带(hUC)-间充质干细胞-EXOs。使用细胞计数试剂盒-8(CCK-8)、Transwell和集落形成试验评估CRC细胞的活性。测量葡萄糖消耗、乳酸生成和细胞外酸化率(ECAR)以评估糖酵解活性。细胞干性通过球形成试验进行评估。此外,还利用 EVmiRNA 数据库分析了 CRC 组织中的间充质干细胞外微RNA(miRNA),并从基因表达总库(GEO)数据库中获得了 CRC 细胞中异常表达的 miRNA。利用Starbase数据库预测了miR-486-5p与从未有丝分裂基因A相关激酶2(NEK2)之间的结合关系,并通过RNA结合蛋白免疫沉淀(RIP)和双荧光素酶测定进行了验证。这些结果表明,hUC-间充质干细胞-EXOs抑制了CRC细胞的增殖和转移。miR-486-5p直接与NEK2结合。过表达 NEK2 逆转了 miR-486-5p 对 CRC 细胞糖酵解和干性的抑制作用。我们的研究表明,hUC-MSC-EXO miR-486-5p通过靶向NEK2抑制了CRC细胞的糖酵解和细胞干性。 这一发现为hUC-MSC-EXO在治疗CRC方面的潜在应用提供了有力的证据。
{"title":"Mesenchymal stem cell-derived exosomes carrying miR-486-5p inhibit glycolysis and cell stemness in colorectal cancer by targeting NEK2.","authors":"Facai Cui, Yu Chen, Xiaoyu Wu, Weifeng Zhao","doi":"10.1186/s12885-024-13086-9","DOIUrl":"10.1186/s12885-024-13086-9","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a major global concern. Mesenchymal stem cell-derived exosomes (MSC-EXOs) have demonstrated efficacy as a therapeutic approach for colorectal cancer. However, the precise mechanism by which MSC-EXOs treat colorectal cancer remains unclear. Human umbilical cord (hUC)-MSC-EXOs were isolated and identified. Cell Counting Kit-8 (CCK-8), Transwell, and colony formation assays were used to assess the activity of CRC cells. Glucose consumption, lactic acid production, and extracellular acidification rate (ECAR) were measured to assess glycolytic activity. Cell stemness was assessed using a sphere-formation assay. Furthermore, MSC-exosomal microRNAs (miRNAs) in CRC tissues were analyzed using the EVmiRNA database, and aberrantly expressed miRNAs in CRC cells were obtained from the Gene Expression Omnibus (GEO) database. The binding relationship between miR-486-5p and the never in mitosis gene A-related kinase 2 (NEK2) was predicted using the Starbase database and validated through RNA binding protein immunoprecipitation (RIP) and dual luciferase assays. These results showed that hUC-MSC-EXOs inhibited the proliferation and metastasis of CRC cells. Moreover, glycolysis and stemness abilities of CRC cells also decreased after treatment with hUC-MSC-EXOs. miR-486-5p was found to be enriched in hUC-MSC-EXOs and significantly downregulated in CRC cells. miR-486-5p directly bound to NEK2. Overexpression of NEK2 reversed the inhibitory effect of miR-486-5p on CRC cell glycolysis and stemness. Our study highlights that hUC-MSC-EXO miR-486-5p inhibits glycolysis and cell stemness in CRC by targeting NEK2. This finding offers compelling evidence supporting the potential application of hUC-MSC-EXOs in the treatment of CRC.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"24 1","pages":"1356"},"PeriodicalIF":3.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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