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结直肠癌的免疫学全景:肿瘤微环境、细胞参与者及免疫治疗机会

英文原题:Immunological landscape of colorectal cancer: tumor microenvironment, cellular players and immunotherapeutic opportunities.

查看英文原题

Immunological landscape of colorectal cancer: tumor microenvironment, cellular players and immunotherapeutic opportunities.

PubMed 2025/10/30(内容时间) Front Mol Biosci Q2 · IF 4.4(JCR 2025)

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中文摘要

结直肠癌(CRC)仍然是全球最致命的恶性肿瘤之一,其结局不仅受基因改变的影响,也受肿瘤微环境(TME)复杂性的塑造。TME包括基质细胞和内皮细胞、细胞外基质成分、肠道微生物群,以及多种免疫细胞,它们动态相互作用,影响肿瘤的发生、进展和治疗反应。本综述描绘了CRC的免疫景观,重点阐述了固有免疫细胞——包括肿瘤相关巨噬细胞、NK 细胞、树突状细胞、中性粒细胞和肥大细胞——的双重功能,以及适应性免疫参与者,如细胞毒性T淋巴细胞、辅助性T细胞亚群和B/浆细胞。这些细胞间相互作用促成了免疫学上“热”的微卫星高度不稳定(MSI-H)肿瘤与“冷”的微卫星稳定(MSS)肿瘤之间的异质性,前者对免疫治疗高度敏感,后者则仍然耐药。本文考察了免疫逃逸的关键机制,如癌症免疫编辑、检查点信号传导和外来体介导的通讯,并结合诸如Immunoscore等作为免疫浸润生物标志物的预后工具进行讨论。本文还讨论了新兴的免疫治疗策略,包括检查点阻断、巨噬细胞重编程、NK 细胞激动剂和微生物组调节,并强调它们在CRC管理中的前景和局限性。通过整合当前对免疫-肿瘤相互作用的见解,本综述强调了开发个性化、靶向TME的干预措施以改善CRC结局的机会。

展开英文摘要原文

Colorectal cancer (CRC) remains one of the most lethal malignancies worldwide, with outcomes shaped not only by genetic alterations but also by the complexity of the tumor microenvironment (TME). The TME encompasses stromal and endothelial cells, extracellular matrix components, gut microbiota, and a diverse array of immune cells that dynamically interact to influence tumor initiation, progression, and therapeutic response. This review delineates the immunological landscape of CRC, highlighting the dual functions of innate immune cells-including tumor-associated macrophages, natural killer cells, dendritic cells, neutrophils, and mast cells-and adaptive immune players such as cytotoxic T lymphocytes, helper T-cell subsets, and B/plasma cells.

These cellular interactions contribute to the heterogeneity between immunologically "hot" microsatellite instability-high (MSI-H) tumors, which are highly responsive to immunotherapy, and "cold" microsatellite-stable (MSS) tumors, which remain resistant. Key mechanisms of immune evasion, such as cancer immunoediting, checkpoint signaling, and exosome-mediated communication, are examined alongside prognostic tools like the Immunoscore that serve as biomarkers of immune infiltration.

Emerging immunotherapeutic strategies, including checkpoint blockade, macrophage reprogramming, natural killer cell agonists, and microbiome modulation, are discussed with emphasis on both their promise and limitations in CRC management. By integrating current insights into immune-tumor interactions, the review underscores opportunities for developing personalized, TME-targeted interventions to improve CRC outcomes.

论文信息

作者
Andac-Aktas AB、Calibasi-Kocal G
第一作者单位
Department of Oncology, Institute of Health Sciences, Dokuz Eylul University, Izmir, Türkiye.Turkey
通讯作者单位
Department of Translational Oncology, Institute of Oncology, Dokuz Eylul University, Izmir, Türkiye.Turkey
文献类型
综述
期刊
Frontiers in molecular biosciences2025
原文标识
PubMed 41244711 · DOI 10.3389/fmolb.2025.1687556