Heregger Ronald, Huemer Florian, Steiner Markus, Gonzalez-Martinez Alejandra, Greil Richard, Weiss Lukas
Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute-Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Center for Clinical Cancer and Immunology Trials (CCCIT), Paracelsus Medical University, 5020 Salzburg, Austria.
Cancer Cluster Salzburg, 5020 Salzburg, Austria.
Cancers (Basel). 2023 Oct 21;15(20):5090. doi: 10.3390/cancers15205090.
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每年都在上升，因此需要有效的治疗策略。免疫检查点抑制剂（ICI）在包括结直肠癌在内的各种癌症中已显示出显著的临床疗效。然而，它们在结直肠癌中的有效性仅限于错配修复缺陷（dMMR）/微卫星高度不稳定（MSI-H）疾病的患者，这类患者约占所有局限性结直肠癌病例的15%，仅占转移性结直肠癌病例的3%至5%。然而，患者之间的反应各不相同，有些患者表现出耐药性或原发性肿瘤进展，这凸显了深入了解潜在机制的必要性。迄今为止，尚未完全了解影响对ICI反应的因素，如肿瘤微环境、免疫细胞、基因变化以及肠道微生物群的影响。本综述旨在探讨dMMR/MSI-H结直肠癌中对ICI的潜在耐药或免疫逃逸机制以及相关细胞类型，以及该特定亚型诊断中可能存在的陷阱。
