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肿瘤微环境如何调节结直肠癌浸润淋巴细胞的募集和激活

英文原题:How the Tumor Micromilieu Modulates the Recruitment and Activation of Colorectal Cancer-Infiltrating Lymphocytes.

查看英文原题

How the Tumor Micromilieu Modulates the Recruitment and Activation of Colorectal Cancer-Infiltrating Lymphocytes.

PubMed 2022/11/15(内容时间) Biomedicines Q2 · IF 4.5(JCR 2025)

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中文摘要

晚期结直肠癌的成功治疗仍然是一个尚未充分解决的临床难题,而大多数恶性结肠肿瘤仅表现出相对较低的免疫原性,因此对免疫治疗方法(例如检查点抑制剂的使用)的反应性有限,这进一步增加了问题的复杂性。过去二十年来已经充分证实,局部肿瘤微环境,特别是瘤内免疫细胞的数量、质量和活化状态,对结直肠癌患者的临床预后及其从免疫治疗中获得的个体化获益具有关键性影响,因此,增强细胞溶解性效应T淋巴细胞及其他抗肿瘤免疫应答细胞介质在瘤内的聚集已成为一个靶向目标。为了未来新型治疗靶结构的识别和临床验证,进一步阐明肠道肿瘤微环境中关键参与免疫细胞募集和活化的分子机制及细胞间相互作用将至关重要。在此背景下,我们的综述文章旨在概述肿瘤微环境中存在并相关性地调节TIL(肿瘤浸润淋巴细胞)数量组成和抗肿瘤能力的关键趋化因子和细胞因子。

展开英文摘要原文

The successful treatment of advanced colorectal cancer disease still represents an insufficiently solved clinical challenge, which is further complicated by the fact that the majority of malignant colon tumors show only relatively low immunogenicity and therefore have only limited responsiveness to immunotherapeutic approaches, such as, for instance, the use of checkpoint inhibitors. As it has been well established over the past two decades that the local tumor microenvironment and, in particular, the quantity, quality, and activation status of intratumoral immune cells critically influence the clinical prognosis of patients diagnosed with colorectal cancer and their individual benefits from immunotherapy, the enhancement of the intratumoral accumulation of cytolytic effector T lymphocytes and other cellular mediators of the antitumor immune response has emerged as a targeted objective.

For the future identification and clinical validation of novel therapeutic target structures, it will thus be essential to further decipher the molecular mechanisms and cellular interactions in the intestinal tumor microenvironment, which are crucially involved in immune cell recruitment and activation. In this context, our review article aims at providing an overview of the key chemokines and cytokines whose presence in the tumor micromilieu relevantly modulates the numeric composition and antitumor capacity of tumor-infiltrating lymphocytes.

论文信息

作者
Atreya I、Neurath MF
单位
Department of Medicine 1, Erlangen University Hospital, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany.Germany
文献类型
综述
期刊
Biomedicines2022 Nov 15
原文标识
PubMed 36428508 · DOI 10.3390/biomedicines10112940