前列腺癌的免疫微环境:全面回顾。

IF 2.5 3区 医学 Q3 ONCOLOGY Oncology Pub Date : 2024-10-09 DOI:10.1159/000541881
Rene Novysedlak, Miray Guney, Majd Al Khouri, Robin Bartolini, Lily Koumbas Foley, Iva Benesova, Andrej Ozaniak, Vojtech Novak, Stepan Vesely, Pavel Pacas, Tomas Buchler, Zuzana Ozaniak Strizova
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引用次数: 0

摘要

背景:前列腺癌(PCa)是一种具有明显免疫抑制特性和免疫激活受限的恶性肿瘤。这种免疫抑制与细胞毒性 T 细胞活性降低、抗原递呈受损以及免疫抑制细胞因子和免疫检查点分子水平升高有关。研究表明,细胞毒性 CD8+ T 细胞浸润与生存率的提高相关,而调节性 T 细胞(Tregs)和肿瘤相关巨噬细胞(TAMs)的增加则与治疗效果和耐药性的恶化相关。Th1细胞是有益的,而产生白细胞介素-17(IL-17)的Th17细胞则会导致肿瘤进展。肿瘤相关中性粒细胞(TANs)和免疫检查点分子(如PD-1/PD-L1和TIM-3)也与PCa晚期有关。化疗有望通过消耗免疫抑制细胞和增强肿瘤免疫原性,将 "冷 "的肿瘤微环境(TME)转化为 "热 "的肿瘤微环境。摘要:这篇综述探讨了 PCa 的免疫微环境,重点关注 TME 中免疫细胞和肿瘤细胞之间错综复杂的相互作用。它强调了TAMs、Tregs、细胞毒性T细胞和其他免疫细胞类型是如何促进或抑制肿瘤发展的,以及PCa的低免疫原性是如何使免疫疗法复杂化的:细胞毒性 CD8+ T 细胞和 Th1 细胞的浸润与更好的治疗效果相关,而 Tregs 和 TAMs 的升高会促进肿瘤生长、转移和抗药性。TANs和NK细胞具有双重作用,NK细胞水平越高,预后越好。PD-1、PD-L1 和 TIM-3 等免疫检查点分子与晚期疾病相关。化疗可以通过消耗Tregs和MDSCs来改善肿瘤的免疫原性,从而带来治疗前景。
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The Immune Microenvironment in Prostate Cancer: A Comprehensive Review.

Background: Prostate cancer (PCa) is a malignancy with significant immunosuppressive properties and limited immune activation. This immunosuppression is linked to reduced cytotoxic T cell activity, impaired antigen presentation, and elevated levels of immunosuppressive cytokines and immune checkpoint molecules. Studies demonstrate that cytotoxic CD8+ T cell infiltration correlates with improved survival, while increased regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) are associated with worse outcomes and therapeutic resistance. Th1 cells are beneficial, whereas Th17 cells, producing interleukin-17 (IL-17), contribute to tumor progression. Tumor-associated neutrophils (TANs) and immune checkpoint molecules, such as PD-1/PD-L1 and T cell immunoglobulin-3 (TIM-3) are also linked to advanced stages of PCa. Chemotherapy holds promise in converting the "cold" tumor microenvironment (TME) to a "hot" one by depleting immunosuppressive cells and enhancing tumor immunogenicity.

Summary: This comprehensive review examines the immune microenvironment in PCa, focusing on the intricate interactions between immune and tumor cells in the TME. It highlights how TAMs, Tregs, cytotoxic T cells, and other immune cell types contribute to tumor progression or suppression and how PCa's low immunogenicity complicates immunotherapy.

Key messages: The infiltration of cytotoxic CD8+ T cells and Th1 cells correlates with better outcomes, while elevated T regs and TAMs promote tumor growth, metastasis, and resistance. TANs and natural killer (NK) cells exhibit dual roles, with higher NK cell levels linked to better prognoses. Immune checkpoint molecules like PD-1, PD-L1, and TIM-3 are associated with advanced disease. Chemotherapy can improve tumor immunogenicity by depleting T regs and myeloid-derived suppressor cells, offering therapeutic promise.

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来源期刊
Oncology
Oncology 医学-肿瘤学
CiteScore
6.00
自引率
2.90%
发文量
76
审稿时长
6-12 weeks
期刊介绍: Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.
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