Over the past decade, immune checkpoint inhibitors (ICI) have proven to be promising agents in a number of solid tumor malignancies. Pembrolizumab and nivolumab are ICIs that target programmed cell death protein 1 and both have been approved by the US Food and Drug Administration for the treatment of microsatellite instability-high/DNA mismatch repair deficient (MSI-H/dMMR) colorectal cancer (CRC). In MSI-H/dMMR CRC, these agents were found to have considerable antitumor activity and are now used in the treatment of this disease. However, MSI-H/dMMR tumors account for only 5% of metastatic CRC and the remaining patients are identified as being microsatellite stable/DNA mismatch repair proficient (MSS/pMMR). In MSS/pMMR CRC, ICIs were found to have no antitumor activity and they are not currently used in the treatment of the disease. However, ongoing research is expanding our knowledge of how the human immune system interacts with cancer cells. Identifying mechanisms to improve our immune response to MSS/pMMR CRC is of utmost importance. In this review, we discuss available clinical data and the emerging role of immune-based strategies to overcome the resistance to ICI therapy in the treatment of MSS/pMMR CRC.

中文翻译：

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免疫检查点抑制剂在结直肠腺癌中的作用。

在过去的十年中，免疫检查点抑制剂（ICI）已被证明是许多实体瘤恶性肿瘤中有希望的药物。Pembrolizumab和nivolumab是靶向程序性细胞死亡蛋白1的ICI，并且均已获得美国食品和药物管理局的批准，可用于治疗微卫星不稳定性高/ DNA错配修复缺陷（MSI-H / dMMR）大肠癌（CRC）。在MSI-H / dMMR CRC中，发现这些药物具有相当大的抗肿瘤活性，目前已用于治疗该疾病。然而，MSI-H / dMMR肿瘤仅占转移性CRC的5％，其余患者被鉴定为微卫星稳定/ DNA错配修复熟练（MSS / pMMR）。在MSS / pMMR CRC中，发现ICI不具有抗肿瘤活性，并且目前尚未用于治疗该疾病。然而，正在进行的研究正在扩展我们对人类免疫系统如何与癌细胞相互作用的知识。确定改善我们对MSS / pMMR CRC的免疫反应的机制至关重要。在这篇综述中，我们讨论了可用的临床数据以及基于免疫的策略在克服MSI / pMMR CRC治疗中对ICI治疗的耐药性方面的新兴作用。