pMMR-MSS/MSI-L Colorectal Cancer: Latest Advances and Future Directions in Immunotherapy—A Review

免疫检查点抑制剂(ICIs)在治疗多种晚期实体肿瘤中的成功，引发了其在结直肠癌(CRC)治疗中的广泛关注。ICIs在具有错配修复缺陷(dMMR)和微卫星高度不稳定(MSI-H) CRC患者中表现出一定疗效。因此FDA加速批准了两种PD-1抑制抗体(anti-PD-1)，帕博利珠单抗(Pembrolizumab)和纳武立珠单抗(Nivolumab)用于dMMR/MSI-H CRC的治疗。相反，具有错配修复正常(pMMR)和微卫星稳定/微卫星低度不稳定(MSS/MSI-L)的患者通常表现出较少的肿瘤浸润淋巴细胞(TILs)，对免疫治疗的反应较差。这些不同的肿瘤微环境突显了肿瘤–免疫相互作用的复杂性，以及将ICIs的效果扩展到大多数CRC患者的挑战。最近的研究表明，ICIs在CRC患者中可能具有潜在获益，这提示了ICIs在CRC领域更广泛的应用前景。本文介绍了这些进展，并探讨了pMMR-MSS/MSI-L CRC中ICIs的未来发展方向。The success of immune checkpoint inhibitors (ICIs) in treating various advanced solid tumors has spurred considerable interest in their application for colorectal cancer (CRC) therapy. ICIs have demonstrated clinical efficacy in CRC patients with deficient mismatch repair (dMMR) and high microsatellite instability (MSI-H). Consequently, the FDA granted accelerated approval to two anti-PD-1 antibodies—pembrolizumab and nivolumab—for treating dMMR/MSI-H CRC. In contrast, patients with proficient mismatch repair (pMMR) and microsatellite stable/low instability (MSS/MSI-L) tumors typically exhibit fewer tumor-infiltrating lymphocytes (TILs) and demonstrate poorer responses to immunotherapy. These distinct tumor microenvironments highlight the complexity of tumor-immune interactions and the challenges in extending ICI benefits to the majority of CRC patients. Recent studies suggest potential therapeutic benefits of ICIs in CRC, indicating broader clinical applications. This article reviews these advances and explores future directions for ICI therapy in pMMR-MSS/MSI-L CRC.