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TIL(肿瘤浸润淋巴细胞)在消化道肿瘤中的作用分子机制与临床应用:综合性综述及面向个体化医疗的未来展望

英文原题:The molecular mechanism of actions and clinical utilities of tumor infiltrating lymphocytes in gastrointestinal cancers: a comprehensive review and future prospects toward personalized medicine.

PubMed 2023/11/24(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

胃肠道(GI)肿瘤仍是重大的全球健康负担,占据了相当数量的发病和死亡病例。

中文摘要

胃肠道(GI)癌症仍是重大的全球健康负担,造成大量病例和死亡。遗憾的是,可靠生物标志物不足,妨碍了对GI癌症患者预后的准确预测,也使治疗顺序难以合理选择,导致许多患者结局不理想。TIL(肿瘤浸润淋巴细胞)与肿瘤免疫微环境(TIME)之间复杂的相互作用,已被证明是多种癌症抗癌治疗应答及相应临床结局的关键决定因素。因此,全球范围内越来越关注将TIL评估作为有前景的肿瘤预后生物标志物,其有望显著改善临床决策。此外,近期免疫治疗领域的发现逐渐改变了癌症治疗格局,并显著延长晚期癌症患者生存。不过,即使实体瘤患者的TIL图谱相似,其应答率仍然受限,因此需要进一步了解TIME与肿瘤之间的细胞和分子串扰。本综述全面总结了阐明TIL潜在分子发病机制、预后意义及其在GI癌症免疫治疗中相关性的现有文献。我们指出,不同TIL亚群的类型、密度和空间分布对预测抗癌治疗应答及患者生存具有关键意义。本综述还强调TIL在调节不同分子亚型治疗应答中的重要作用,例如GI癌症中微卫星稳定或程序性细胞死亡配体1表达相关亚型。最后,我们概述TIL个体化医疗的未来方向,包括将TIL方法纳入现有治疗方案,以及开发利用TIL独特特征和潜力的新疗法,以推动个体化癌症治疗。

展开英文摘要原文

Gastrointestinal (GI) cancers remain a significant global health burden, accounting for a substantial number of cases and deaths. Regrettably, the inadequacy of dependable biomarkers hinders the precise forecasting of patient prognosis and the selection of appropriate therapeutic sequencing for individuals with GI cancers, leading to suboptimal outcomes for numerous patients. The intricate interplay between tumor-infiltrating lymphocytes (TILs) and the tumor immune microenvironment (TIME) has been shown to be a pivotal determinant of response to anti-cancer therapy and consequential clinical outcomes across a multitude of cancer types. Therefore, the assessment of TILs has garnered global interest as a promising prognostic biomarker in oncology, with the potential to improve clinical decision-making substantially. Moreover, recent discoveries in immunotherapy have progressively changed the landscape of cancer treatment and significantly prolonged the survival of patients with advanced cancers. Nonetheless, the response rate remains constrained within solid tumor sufferers, even when TIL landscapes appear comparable, which calls for the development of our understanding of cellular and molecular cross-talk between TIME and tumor. Hence, this comprehensive review encapsulates the extant literature elucidating the TILs' underlying molecular pathogenesis, prognostic significance, and their relevance in the realm of immunotherapy for patients afflicted by GI tract cancers. Within this review, we demonstrate that the type, density, and spatial distribution of distinct TIL subpopulations carries pivotal implications for the prediction of anti-cancer treatment responses and patient survival. Furthermore, this review underscores the indispensable role of TILs in modulating therapeutic responses within distinct molecular subtypes, such as those characterized by microsatellite stability or programmed cell death ligand-1 expression in GI tract cancers. The review concludes by outlining future directions in TIL-based personalized medicine, including integrating TIL-based approaches into existing treatment regimens and developing novel therapeutic strategies that exploit the unique properties of TILs and their potential as a promising avenue for personalized cancer treatment.

论文信息

作者
Piroozkhah M、Gholinezhad Y、Piroozkhah M、Shams E、Nazemalhosseini-Mojarad E
第一作者单位
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Iran
通讯作者单位
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Iran
文献类型
综述
期刊
Frontiers in immunology2023
原文标识
PubMed 38077386 · DOI 10.3389/fimmu.2023.1298891