Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths. Incidences of early CRC cases are increasing annually in high-income countries, necessitating effective treatment strategies. Immune checkpoint inhibitors (ICIs) have shown significant clinical efficacy in various cancers, including CRC. However, their effectiveness in CRC is limited to patients with mismatch-repair-deficient (dMMR)/microsatellite instability high (MSI-H) disease, which accounts for about 15% of all localized CRC cases and only 3% to 5% of metastatic CRC cases. However, the varied response among patients, with some showing resistance or primary tumor progression, highlights the need for a deeper understanding of the underlying mechanisms. Elements involved in shaping the response to ICIs, such as tumor microenvironment, immune cells, genetic changes, and the influence of gut microbiota, are not fully understood thus far. This review aims to explore potential resistance or immune-evasion mechanisms to ICIs in dMMR/MSI-H CRC and the cell types involved, as well as possible pitfalls in the diagnosis of this particular subtype.
结直肠癌（CRC）是全球第三大常见癌症，也是癌症相关死亡的第二大主要原因。在高收入国家，早期结直肠癌病例的发病率逐年上升，因此迫切需要有效的治疗策略。免疫检查点抑制剂（ICIs）在包括结直肠癌在内的多种癌症中显示出显著的临床疗效。然而，其在结直肠癌中的有效性仅限于错配修复缺陷（dMMR）/微卫星不稳定性高（MSI-H）的患者，这类患者约占所有局部结直肠癌病例的15%，而在转移性结直肠癌病例中仅占3%至5%。然而，患者对治疗的反应存在差异，部分患者表现出耐药性或原发性肿瘤进展，这突显了深入理解其潜在机制的必要性。目前，影响ICIs反应的因素，如肿瘤微环境、免疫细胞、遗传变化以及肠道微生物群的影响，尚未完全阐明。本综述旨在探讨dMMR/MSI-H结直肠癌中对ICIs的潜在耐药或免疫逃逸机制及其涉及的细胞类型，以及诊断这一特定亚型时可能存在的陷阱。
Unraveling Resistance to Immunotherapy in MSI-High Colorectal Cancer
肿瘤(癌症)患者之家