Division of Hematology and Medical Oncology, Mayo Clinic Cancer Center, Mayo Clinic Hospital, 5777 E Mayo Blvd, Phoenix, AZ, 85054, USA.
BioDrugs. 2020 Jun;34(3):349-362. doi: 10.1007/s40259-020-00420-3.
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.
在过去的十年中，免疫检查点抑制剂（ICI）已被证明在许多实体瘤恶性肿瘤中是有前途的药物。Pembrolizumab 和 nivolumab 是针对程序性细胞死亡蛋白 1 的 ICI，均已被美国食品和药物管理局批准用于治疗微卫星不稳定/DNA 错配修复缺陷（MSI-H/dMMR）结直肠癌（CRC）。在 MSI-H/dMMR CRC 中，这些药物被发现具有相当大的抗肿瘤活性，现在用于治疗这种疾病。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 错配修复正常（MSS/pMMR）。在 MSS/pMMR CRC 中，ICI 被发现没有抗肿瘤活性，目前不用于治疗该疾病。然而，正在进行的研究正在扩展我们对人体免疫系统与癌细胞相互作用的认识。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，我们讨论了现有的临床数据和新兴的免疫策略在克服 MSS/pMMR CRC 的 ICI 治疗耐药性中的作用。
