Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Cells. 2020 Mar 4;9(3):618. doi: 10.3390/cells9030618.
Colorectal cancer (CRC) is the third most common cancer type, and third highest in mortality rates among cancer-related deaths in the United States. Originating from intestinal epithelial cells in the colon and rectum, that are impacted by numerous factors including genetics, environment and chronic, lingering inflammation, CRC can be a problematic malignancy to treat when detected at advanced stages. Chemotherapeutic agents serve as the historical first line of defense in the treatment of metastatic CRC. In recent years, however, combinational treatment with targeted therapies, such as vascular endothelial growth factor, or epidermal growth factor receptor inhibitors, has proven to be quite effective in patients with specific CRC subtypes. While scientific and clinical advances have uncovered promising new treatment options, the five-year survival rate for metastatic CRC is still low at about 14%. Current research into the efficacy of immunotherapy, particularly immune checkpoint inhibitor therapy (ICI) in mismatch repair deficient and microsatellite instability high (dMMR-MSI-H) CRC tumors have shown promising results, but its use in other CRC subtypes has been either unsuccessful, or not extensively explored. This Review will focus on the current status of immunotherapies, including ICI, vaccination and adoptive T cell therapy (ATC) in the treatment of CRC and its potential use, not only in dMMR-MSI-H CRC, but also in mismatch repair proficient and microsatellite instability low (pMMR-MSI-L).
结直肠癌(CRC)是美国第三大常见癌症类型,也是癌症相关死亡中死亡率第三高的癌症。它起源于结肠和直肠的肠上皮细胞,受遗传、环境和慢性、持续的炎症等多种因素影响。当在晚期发现时,CRC 可能是一种难以治疗的恶性肿瘤。化疗药物是治疗转移性 CRC 的历史上的一线防御手段。然而,近年来,联合使用靶向治疗药物,如血管内皮生长因子或表皮生长因子受体抑制剂,已被证明对特定 CRC 亚型的患者非常有效。尽管科学和临床进展揭示了有前途的新治疗选择,但转移性 CRC 的五年生存率仍较低,约为 14%。目前对免疫疗法(特别是免疫检查点抑制剂疗法[ICI])在错配修复缺陷和微卫星不稳定高(dMMR-MSI-H)CRC 肿瘤中的疗效的研究显示出了有希望的结果,但在其他 CRC 亚型中的应用要么不成功,要么没有得到广泛探索。这篇综述将重点介绍免疫疗法的现状,包括 ICI、疫苗接种和过继性 T 细胞疗法(ATC)在 CRC 治疗中的应用,以及其潜在用途,不仅在 dMMR-MSI-H CRC 中,而且在错配修复完整和微卫星不稳定低(pMMR-MSI-L)CRC 中。