Cancer letters最新文献_第2页

Functional diversity and regulation of IL-9-producing T cells in cancer immunotherapy. 癌症免疫疗法中产生 IL-9 的 T 细胞的功能多样性和调节。

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters

Pub Date : 2024-10-17 DOI: 10.1016/j.canlet.2024.217306

Muhammad Kalim, Rui Jing, Wei Guo, Hui Xing, Yong Lu

IL-9-producing T cells (T9) regulate immunological responses that affect various cellular biological processes, though their precise function remains fully understood. Previous studies have linked T9 cells to conditions such as allergic disorders, parasitic infection clearance, and various types of cancers. While the functional heterogeneity of IL-9 and T9 cells in cancer development has been documented, these cells present promising therapeutic opportunities for treating solid tumors. This review highlights the roles of IL-9 and T9 cells in cancer progression and treatment responses, focusing on potential discrepancies in IL-9/IL-9R signaling between murine tumors and cancer patients. Additionally, we discuss the regulation of tumor-specific Th9/Tc9 cell differentiation, the therapeutic potential of these cells, and current strategies to enhance their anti-tumor activities.

产生 IL-9 的 T 细胞（T9）可调节影响各种细胞生物过程的免疫反应，但它们的确切功能仍有待全面了解。以前的研究已将 T9 细胞与过敏性疾病、寄生虫感染清除和各种癌症等病症联系起来。虽然 IL-9 和 T9 细胞在癌症发展中的功能异质性已被记录在案，但这些细胞为治疗实体瘤提供了大有可为的治疗机会。本综述强调了IL-9和T9细胞在癌症进展和治疗反应中的作用，重点研究了小鼠肿瘤和癌症患者之间IL-9/IL-9R信号传导的潜在差异。此外，我们还讨论了肿瘤特异性 Th9/Tc9 细胞分化的调控、这些细胞的治疗潜力以及增强其抗肿瘤活性的当前策略。

引用次数: 0

LncRNAs and the cancer epigenome: Mechanisms and therapeutic potential LncRNAs 与癌症表观基因组：机制与治疗潜力》。

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters

Pub Date : 2024-10-16 DOI: 10.1016/j.canlet.2024.217297

Long non-coding RNAs (lncRNAs) have emerged as critical regulators of epigenome, modulating gene expression through DNA methylation, histone modification, and/or chromosome remodeling. Dysregulated lncRNAs act as oncogenes or tumor suppressors, driving tumor progression by shaping the cancer epigenome. By interacting with the writers, readers, and erasers of the epigenetic script, lncRNAs induce epigenetic modifications that bring about changes in cancer cell proliferation, apoptosis, epithelial-mesenchymal transition, migration, invasion, metastasis, cancer stemness and chemoresistance. This review analyzes and discusses the multifaceted role of lncRNAs in cancer pathobiology, from cancer genesis and progression through metastasis and therapy resistance. It also explores the therapeutic potential of targeting lncRNAs through innovative diagnostic, prognostic, and therapeutic strategies. Understanding the dynamic interplay between lncRNAs and epigenome is crucial for developing personalized therapeutic strategies, offering new avenues for precision cancer medicine.

长非编码 RNA（lncRNA）已成为表观基因组的关键调控因子，通过 DNA 甲基化、组蛋白修饰和/或染色体重塑调节基因表达。失调的lncRNA可作为致癌基因或肿瘤抑制因子，通过塑造癌症表观基因组来推动肿瘤进展。通过与表观遗传学剧本的撰写者、阅读者和擦除者相互作用，lncRNA诱导表观遗传学修饰，从而导致癌细胞增殖、凋亡、上皮-间质转化、迁移、侵袭、转移、癌症干性和化疗耐药性的改变。这篇综述分析和讨论了 lncRNA 在癌症病理生物学中的多方面作用，包括癌症的发生、发展、转移和耐药性。它还探讨了通过创新诊断、预后和治疗策略靶向 lncRNAs 的治疗潜力。了解 lncRNA 与表观基因组之间的动态相互作用对于开发个性化治疗策略至关重要，为癌症精准医疗提供了新途径。

引用次数: 0

The eIF3a translational control axis in the Wnt/β-catenin signaling pathway and colon tumorigenesis Wnt/β-catenin信号通路中的eIF3a翻译控制轴与结肠肿瘤发生。

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters

Pub Date : 2024-10-15 DOI: 10.1016/j.canlet.2024.217303

Translational initiation in protein synthesis is an important regulatory step in gene expression and its dysregulation may result in diseases such as cancer. Translational control by eIF4E/4E-BP has been well studied and contributes to mTOR signaling in various biological processes. Here, we report a novel translational control axis in the Wnt/β-catenin signaling pathway in colon tumorigenesis by eIF3a, a Yin-Yang factor in tumorigenesis and prognosis. We show that eIF3a expression is upregulated in human colon cancer tissues, pre-cancerous adenoma polyps, and associates with β-catenin level and APC mutation in human samples, and that eIF3a overexpression transforms intestinal epithelial cells. We also show that eIF3a expression is regulated by the Wnt/β-catenin signaling pathway with an active TCF/LEF binding site in its promoter and that eIF3a knockdown inhibits APC mutation-induced spontaneous colon tumorigenesis in APC^min/+ mice. Together, we conclude that eIF3a upregulation in colon cancer is due to APC mutation and it participates in colon tumorigenesis by adding a translational control axis in the Wnt/β-catenin signaling pathway and that it can serve as a potential target for colon cancer intervention.

蛋白质合成中的转化起始是基因表达的重要调控步骤，其失调可能导致癌症等疾病。eIF4E/4E-BP 的翻译控制已被深入研究，并在各种生物过程中对 mTOR 信号转导做出了贡献。在这里，我们报告了结肠肿瘤发生过程中 Wnt/β-catenin 信号通路中一个新的转译控制轴，即肿瘤发生和预后的阴阳因子 eIF3a。我们发现，eIF3a在人类结肠癌组织、癌前腺瘤息肉中表达上调，并与人类样本中的β-catenin水平和APC突变相关，eIF3a的过表达可转化肠上皮细胞。我们还发现，eIF3a的表达受Wnt/β-catenin信号通路调控，其启动子中有一个活跃的TCF/LEF结合位点，敲除eIF3a可抑制APC突变诱导的APCmin/+小鼠自发性结肠肿瘤发生。综上所述，我们得出结论：eIF3a在结肠癌中的上调是由于APC突变引起的，它通过在Wnt/β-catenin信号通路中增加一个翻译控制轴参与结肠癌的发生，可以作为结肠癌干预的潜在靶点。

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引用次数: 0

Evaluation of glucocorticoid-related genes reveals GPD1 as a therapeutic target and regulator of sphingosine 1-phosphate metabolism in CRPC 对糖皮质激素相关基因的评估显示 GPD1 是 CRPC 的治疗靶点和 1-磷酸鞘磷脂代谢的调节器。

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters

Pub Date : 2024-10-15 DOI: 10.1016/j.canlet.2024.217286

Prostate cancer (PCa) is an androgen-dependent disease, with castration-resistant prostate cancer (CRPC) being an advanced stage that no longer responds to androgen deprivation therapy (ADT). Mounting evidence suggests that glucocorticoid receptors (GR) confer resistance to ADT in CRPC patients by bypassing androgen receptor (AR) blockade. GR, as a novel therapeutic target in CRPC, has attracted substantial attention worldwide. This study utilized bioinformatic analysis of publicly available CRPC single-cell data to develop a consensus glucocorticoid-related signature (Glu-sig) that can serve as an independent predictor for relapse-free survival. Our results revealed that the signature demonstrated consistent and robust performance across seven publicly accessible datasets and an internal cohort. Furthermore, our findings demonstrated that glycerol-3-phosphate dehydrogenase 1 (GPD1) in Glu-sig can significantly promote CRPC progression by mediating the cell cycle pathway. Additionally, GPD1 was shown to be regulated by GR, with the GR antagonist mifepristone enhancing the anti-tumorigenic effects of GPD1 in CRPC cells. Mechanistically, targeting GPD1 induced the production of sphingosine 1-phosphate (S1P) and enhanced histone acetylation, thereby inducing the transcription of p21 that involved in cell cycle regulation. In conclusion, Glu-sig could serve as a robust and promising tool to improve the clinical outcomes of PCa patients, and modulating the GR/GPD1 axis that promotes tumor growth may be a promising approach for delaying CRPC progression.

前列腺癌（PCa）是一种雄激素依赖性疾病，其中阉割耐药前列腺癌（CRPC）是对雄激素剥夺疗法（ADT）不再有反应的晚期前列腺癌。越来越多的证据表明，糖皮质激素受体（GR）通过绕过雄激素受体（AR）阻断作用，使CRPC患者对ADT产生耐药性。GR作为CRPC的新型治疗靶点，在全球范围内引起了广泛关注。本研究利用生物信息学分析公开的CRPC单细胞数据，建立了一个共识的糖皮质激素相关特征（Glu-sig），该特征可作为无复发生存的独立预测指标。我们的研究结果表明，该特征在七个可公开获取的数据集和一个内部队列中表现出一致且稳健的性能。此外，我们的研究结果表明，Glu-sig 中的甘油-3-磷酸脱氢酶 1 (GPD1) 可通过介导细胞周期通路显著促进 CRPC 的进展。此外，GPD1还受GR调控，GR拮抗剂米非司酮可增强GPD1在CRPC细胞中的抗肿瘤作用。从机理上讲，靶向 GPD1 可诱导产生 1-磷酸鞘磷脂（S1P）并增强组蛋白乙酰化，从而诱导参与细胞周期调控的 p21 的转录。总之，Glu-sig可以作为一种强大而有前途的工具来改善PCa患者的临床预后，而调节促进肿瘤生长的GR/GPD1轴可能是延缓CRPC进展的一种有前途的方法。

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引用次数: 0

Inhibition of TGF-β signaling in bone marrow endothelial cells promotes hematopoietic recovery in acute myeloid leukemia patients 抑制骨髓内皮细胞中的 TGF-β 信号传导可促进急性髓性白血病患者的造血功能恢复。

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters

Pub Date : 2024-10-11 DOI: 10.1016/j.canlet.2024.217290

Although it is an effective treatment for acute myeloid leukemia (AML), chemotherapy leads to myelosuppression and poor hematopoietic reconstruction. Hematopoiesis is regulated by bone marrow (BM) endothelial cells (ECs), and BM ECs are dysfunctional in acute leukemia patients with poor hematopoietic reconstitution after allogenic hematopoietic stem cell transplantation. Thus, it is crucial to explore the underlying mechanism of EC impairment and establish strategies for targeted therapy. TGF-β signaling was found to be upregulated in ECs from AML patients in complete remission (CR ECs) and led to CR EC damage. Administration of a TGF-β inhibitor rescued the dysfunction of ECs caused by TGF-β1 expression in vitro, especially their hematopoiesis-supporting ability. Moreover, inhibition of TGF-β expression repaired the BM EC damage triggered by chemotherapy in both AML patients in vitro and in an AML-CR murine model, and restored normal hematopoiesis without promoting AML progression. Mechanistically, our data reveal alterations in the transcriptomic pattern of damaged BM ECs, accompanied by the overexpression of downstream molecules TGF-βR1, pSmad2/3, and functional genes related to adhesion, angiogenesis suppression and pro-apoptosis. Collectively, our findings reveal for the first time that the activation of TGF-β signaling leads to BM EC dysfunction and poor hematopoietic reconstitution. Targeting TGF-β represents a potential therapeutic strategy to promote multilineage hematopoiesis, thereby benefiting more cancer patients who suffer from myelosuppression after chemotherapy.

虽然化疗是治疗急性髓性白血病（AML）的有效方法，但化疗会导致骨髓抑制和造血重建不良。造血受骨髓（BM）内皮细胞（EC）调控，急性白血病患者异基因造血干细胞移植后造血重建不良，BM EC功能失调。因此，探索EC受损的内在机制并制定靶向治疗策略至关重要。研究发现，TGF-β信号在完全缓解的急性髓细胞性白血病患者（CR ECs）的ECs中上调，并导致CR EC损伤。服用TGF-β抑制剂可挽救体外TGF-β1表达导致的EC功能障碍，尤其是其造血支持能力。此外，抑制 TGF-β 的表达还能修复急性髓细胞性白血病患者体外和急性髓细胞性白血病-慢性淋巴细胞性白血病鼠模型中化疗引发的骨髓造血干细胞损伤，并恢复正常的造血功能，而不会促进急性髓细胞性白血病的进展。从机理上讲，我们的数据揭示了受损骨髓细胞的转录组模式发生了改变，伴随着下游分子 TGF-βR1、pSmad2/3 以及与粘附、血管生成抑制和促凋亡相关的功能基因的过度表达。总之，我们的研究结果首次揭示了 TGF-β 信号的激活会导致 BM EC 功能障碍和造血重建不良。靶向 TGF-β 是一种促进多系造血的潜在治疗策略，从而使更多化疗后骨髓抑制的癌症患者受益。

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引用次数: 0

Autophagy and cancer therapy 自噬与癌症治疗

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters

Pub Date : 2024-10-10 DOI: 10.1016/j.canlet.2024.217285

Autophagy is an intracellular degradation process that sequesters cytoplasmic components in double-membrane vesicles known as autophagosomes, which are degraded upon fusion with lysosomes. This pathway maintains the integrity of proteins and organelles while providing energy and nutrients to cells, particularly under nutrient deprivation. Deregulation of autophagy can cause genomic instability, low protein quality, and DNA damage, all of which can contribute to cancer. Autophagy can also be overactivated in cancer cells to aid in cancer cell survival and drug resistance. Emerging evidence indicates that autophagy has functions beyond cargo degradation, including roles in tumor immunity and cancer stem cell survival. Additionally, autophagy can also influence the tumor microenvironment. This feature warrants further investigation of the role of autophagy in cancer, in which autophagy manipulation can improve cancer therapies, including cancer immunotherapy. This review discusses recent findings on the regulation of autophagy and its role in cancer therapy and drug resistance.

自噬是一种细胞内降解过程，它将细胞质成分封存在称为自噬体的双膜囊泡中，并在与溶酶体融合后降解。这一途径可维持蛋白质和细胞器的完整性，同时为细胞提供能量和营养物质，尤其是在缺乏营养的情况下。自噬失调会导致基因组不稳定、蛋白质质量低下和 DNA 损伤，所有这些都可能导致癌症。自噬也可能在癌细胞中被过度激活，从而帮助癌细胞存活并产生抗药性。新的证据表明，自噬的功能不仅限于降解货物，还包括在肿瘤免疫和癌症干细胞存活中发挥作用。此外，自噬还能影响肿瘤微环境。这一特点促使人们进一步研究自噬在癌症中的作用，其中自噬操作可改善癌症疗法，包括癌症免疫疗法。本综述将讨论有关自噬调控及其在癌症治疗和耐药性中作用的最新发现。

引用次数: 0

S100A7 orchestrates neutrophil chemotaxis and drives neutrophil extracellular traps (NETs) formation to facilitate lymph node metastasis in cervical cancer patients S100A7 可协调中性粒细胞趋化并推动中性粒细胞胞外捕获物 (NET) 的形成，从而促进宫颈癌患者的淋巴结转移。

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters

Pub Date : 2024-10-09 DOI: 10.1016/j.canlet.2024.217288

Neutrophil extracellular traps (NETs) have been shown to promote the metastatic potential of many kinds of tumors. Our study aimed to investigate the role and mechanisms of NETs in lymph node metastasis (LNM) of cervical cancer (CCa), and evaluated the therapeutic value of targeting NETs in CCa. Immunohistochemistry demonstrated that neutrophil infiltration and NETs formation were increased in CCa patients with LNM, as well as confirming a positive correlation between S100A7 expression and neutrophil infiltration in CCa. NETs enhanced the migratory capability of CCa by activating the P38-MAPK/ERK/NFκB pathway through interaction with TLR2. Digesting NETs with deoxyribonuclease 1 (DNase 1) or inhibiting TLR2 with chloroquine eliminated the NETs-induced metastatic potential of CCa. Additionally, NETs promoted lymphangiogenesis and increased the permeability of lymphatic vessels, thus facilitating translymphatic movement of CCa. CCa-derived S100A7 exhibited a chemotactic effect on neutrophils and promoted NETs generation by elevating ROS levels rather than activating autophagy in neutrophils. The mouse model with footpad implantation illustrated that DNase 1 effectively reduced LNM in LPS-induced mice and in mice seeded with S100A7-overexpressing CCa cells. In conclusion, our study reveals a new tumor-promoting mechanism of S100A7, clarifies the crucial role and mechanism of NETs in LNM of CCa, and indicates that the NETs-targeted therapy emerges as a promising anti-metastasis therapy in CCa.

中性粒细胞胞外捕获物（NET）已被证明能促进多种肿瘤的转移。我们的研究旨在探讨NETs在宫颈癌（CCa）淋巴结转移（LNM）中的作用和机制，并评估靶向NETs在CCa中的治疗价值。免疫组化结果表明，患有LNM的CCa患者中性粒细胞浸润和NETs形成增加，同时证实S100A7表达与CCa中性粒细胞浸润呈正相关。NETs通过与TLR2相互作用激活P38-MAPK/ERK/NFκB通路，从而增强了CCa的迁移能力。用脱氧核糖核酸酶1（DNase 1）消化NETs或用氯喹抑制TLR2可消除NETs诱导的CCa转移潜能。此外，NETs 还能促进淋巴管生成，增加淋巴管的通透性，从而促进 CCa 的跨淋巴运动。CCa衍生的S100A7对中性粒细胞有趋化作用，并通过提高ROS水平而不是激活中性粒细胞的自噬作用促进NET的生成。脚垫植入小鼠模型表明，DNase 1 能有效减少 LPS 诱导的小鼠和播种了 S100A7 高表达 CCa 细胞的小鼠的 LNM。总之，我们的研究揭示了S100A7新的促瘤机制，阐明了NETs在CCa LNM中的关键作用和机制，并指出NETs靶向疗法是一种很有前景的CCa抗转移疗法。

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引用次数: 0

Pirfenidone antagonizes TGF-β1-mediated gabapentin resistance via reversal of desmoplasia and the ‘cold’ microenvironment in pancreatic cancer 吡非尼酮通过逆转胰腺癌的脱落细胞和 "冷 "微环境拮抗TGF-β1介导的加巴喷丁抗性

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters

Pub Date : 2024-10-09 DOI: 10.1016/j.canlet.2024.217287

Owing to the desmoplastic stroma constituted by cancer-associated fibroblasts (CAFs), few immune cells infiltrate the pancreatic ductal adenocarcinoma (PDAC). Gabapentin can impede the production of ketoacids by CAFs to support cancer cells. However, in our study, we discovered a dose-dependent increase in transforming growth factor β1 (TGF-β1) levels in cancer cells in response to gabapentin. This reverse increase of TGF-β1 contributes to 'Gabapentin-resistance', leading to the antitumor effects on PDAC cell lines are negatively negotiated in the presence of pancreatic stellate cells. Pirfenidone synergistically inhibited the growth and apoptosis resistance of PDAC when combined with Gabapentin. In a mouse orthotopic PDAC model, Fe³⁺-mediated coordination nanodrugs, which contain gabapentin, pirfenidone and the natural polyphenol (EGCG), efficiently promoted the infiltration of naïve CD8⁺ T cells (CD44^lowCD62L^high) and the accumulation of inflammatory CAFs (α-SMA^lowIL-6^high). This led to a nearly two-fold increase in survival compared to the control. Furthermore, we identified a new subpopulation as Hmox1^highiCAFs following treatment with our nanodrugs. Hmox1^highiCAFs overexpressed the Cxcl10 receptor (Sdc4) and facilitated functional CD8⁺ T-cell infiltration through the Tnfsf9-Tnfrsf9 axis. Overall, our nanodrugs reshape the phenotype of CAFs and enhance functional CD8⁺ T-cell infiltration into tumors, holding the potential to be a safe and promising therapy for PDAC.

由于胰腺导管腺癌（PDAC）的基质由癌相关成纤维细胞（CAFs）构成，很少有免疫细胞浸润其中。加巴喷丁能阻碍 CAFs 产生酮酸以支持癌细胞。然而，在我们的研究中，我们发现癌细胞中的转化生长因子β1（TGF-β1）水平在加巴喷丁作用下呈剂量依赖性增加。这种 TGF-β1 的反向增加导致了 "加巴喷丁抗药性"，从而导致在胰腺星状细胞存在的情况下，对 PDAC 细胞株的抗肿瘤作用会产生负作用。吡非尼酮与加巴喷丁联合使用时，能协同抑制 PDAC 的生长和凋亡抵抗。在小鼠正位 PDAC 模型中，含有加巴喷丁、吡非尼酮和天然多酚（EGCG）的 Fe3+ 介导配位纳米药物有效促进了幼稚 CD8+ T 细胞（CD44-lowCD62Lhigh）的浸润和炎性 CAFs（α-SMA-lowIL-6high）的聚集。与对照组相比，存活率提高了近两倍。此外，在使用纳米药物治疗后，我们还发现了一个新的亚群，即 Hmox1highiCAFs。Hmox1highiCAFs过度表达Cxcl10受体（Sdc4），并通过Tnfsf9-Tnfrsf9轴促进功能性CD8+T细胞浸润。总之，我们的纳米药物重塑了CAFs的表型，增强了CD8+ T细胞对肿瘤的功能性浸润，有望成为治疗PDAC的一种安全而有前景的疗法。

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引用次数: 0

Pancreatic cancer cell-derived migrasomes promote cancer progression by fostering an immunosuppressive tumor microenvironment 胰腺癌细胞衍生的移行体通过培养免疫抑制性肿瘤微环境促进癌症进展

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters

Pub Date : 2024-10-09 DOI: 10.1016/j.canlet.2024.217289

Pancreatic cancer is distinguished by an immunosuppressive tumor microenvironment (TME) that facilitates cancer progression. The assembly of the TME involves numerous contributing factors. Migrasomes, recently identified as cellular organelles in migrating cells, play a pivotal role in intercellular signaling. However, research into their involvement in cancers remains nascent. Thus far, whether pancreatic cancer cells generate migrasomes and their potential role in TME formation remains unexplored. In this study, it was found that both murine and human pancreatic cancer cells could indeed generate migrasomes, termed pancreatic cancer cell-derived migrasomes (PCDMs), which actively promote cancer progression. Moreover, utilizing chemokine antibody arrays and quantitative mass spectrometry analysis, we observed significant differences between the chemokines, cytokines, and proteins present in PCDMs compared to their originating cell bodies. Notably, PCDMs exhibited an enrichment of immunosuppression-inducing factors. Furthermore, macrophages could directly uptake PCDMs, leading to the expression of high levels of M2-like markers and secretion of tumor-promoting factors. PCDM-induced macrophages played a pivotal role in inhibiting T cell proliferation and activation partially through ARG-1. In summary, this study provides compelling evidence that pancreatic cancer cells generate migrasomes, which play a crucial role in promoting tumor progression by contributing to an immunosuppressive TME. The exploration of migrasomes as a therapeutic target could pave the way for the development of tailored immunotherapies for pancreatic cancer.

胰腺癌的特征是具有免疫抑制作用的肿瘤微环境（TME），这种环境有利于癌症的进展。肿瘤微环境的形成涉及多种因素。移行体（Migrasomes）最近被确认为移行细胞中的细胞器，在细胞间信号传递中发挥着关键作用。然而，有关它们参与癌症的研究仍处于起步阶段。迄今为止，胰腺癌细胞是否产生移行体及其在TME形成过程中的潜在作用仍未得到研究。本研究发现，小鼠和人类胰腺癌细胞确实能产生移行体，即胰腺癌细胞衍生移行体（Pancreatic cancer cell-derived migrasomes，PCDMs），它能积极促进癌症进展。此外，利用趋化因子抗体阵列和定量质谱分析，我们观察到 PCDMs 中的趋化因子、细胞因子和蛋白质与其起源细胞体相比存在显著差异。值得注意的是，PCDM 中富含免疫抑制诱导因子。此外，巨噬细胞可直接吸收 PCDMs，从而导致高水平的 M2 类标志物的表达和肿瘤促进因子的分泌。PCDM 诱导的巨噬细胞部分通过 ARG-1 在抑制 T 细胞增殖和活化方面发挥了关键作用。总之，本研究提供了令人信服的证据，证明胰腺癌细胞会产生移行体，而移行体在促进肿瘤进展的过程中扮演着至关重要的角色，它有助于形成具有免疫抑制作用的TME。将移行体作为治疗靶点进行探索，可为开发针对胰腺癌的定制免疫疗法铺平道路。

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引用次数: 0

Therapeutic potential of tumor-infiltrating lymphocytes in non-small cell lung cancer 肿瘤浸润淋巴细胞在非小细胞肺癌中的治疗潜力。

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters

Pub Date : 2024-10-05 DOI: 10.1016/j.canlet.2024.217281

Lung cancer is the leading cause of cancer-related death worldwide, with poor outcomes even for those diagnosed at early stages. Current standard-of-care for most non-small cell lung cancer (NSCLC) patients involves an array of chemotherapy, radiotherapy, immunotherapy, targeted therapy, and surgical resection depending on the stage and location of the cancer. While patient outcomes have certainly improved, advances in highly personalized care remain limited. However, there is growing excitement around harnessing the power of tumor-infiltrating lymphocytes (TILs) through the use of adoptive cell transfer (ACT) therapy. These TILs are naturally occurring, may already recognize tumor-specific antigens, and can have direct anti-cancer effect. In this review, we highlight comparisons of various ACTs, including a brief TIL history, show current advances and successes of TIL therapy in NSCLC, discuss the potential roles for epigenetics in T cell expansion, and highlight challenges and future directions of the field to combat NSCLC in a personalized manner.

肺癌是全球癌症相关死亡的主要原因，即使是早期诊断的肺癌患者也很难治愈。目前，大多数非小细胞肺癌（NSCLC）患者的标准治疗方法包括一系列化疗、放疗、免疫治疗、靶向治疗和手术切除，具体取决于癌症的分期和位置。虽然患者的治疗效果确实有所改善，但高度个性化治疗的进展仍然有限。不过，通过采用性细胞转移疗法（ACT）利用肿瘤浸润淋巴细胞（TILs）的力量正日益受到人们的关注。这些TIL是天然存在的，可能已经识别出肿瘤特异性抗原，并能产生直接的抗癌效果。在这篇综述中，我们将重点比较各种领养细胞转移疗法，包括简要介绍TIL的历史，展示目前TIL疗法在NSCLC中的进展和成功案例，讨论表观遗传学在T细胞扩增中的潜在作用，并强调该领域在以个性化方式抗击NSCLC方面所面临的挑战和未来发展方向。

引用次数: 0