结直肠癌免疫治疗的现状、挑战和出路

[摘要] 结直肠癌（colorectal cancer，CRC）是世界范围内发病率第3 位、病死率第4 位的恶性肿瘤，现有的临床治疗主要以传统的化疗、放疗、手术治疗和靶向治疗为主，但这些方法对于出现复发或转移的患者的疗效欠佳。近期发展起来的免疫疗法在某些恶性肿瘤（如白血病、黑色素瘤和非小细胞肺癌）的临床试验中显示出较好的疗效，相关的试验也在CRC中开展，但除PD-1 抑制剂在DNA错配修复系统缺陷型CRC中的效果显著外，大部分的临床试验并未达到预期的效果。本文着重介绍CRC不同亚型的免疫表型，总结现有CRC免疫疗法的相关进展，并探讨目前免疫疗法治疗CRC疗效低下可能的原因，在此基础上提出未来可能的解决途径和发展方向。

Immunotherapy for colorectal cancer: current status, challenges and solution

[Abstract] Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer-related death all over the world. Traditional treatments, including chemotherapy, radiation therapy, surgery and targeted therapy, form the backbone of current treatment in various stages of CRC, but the efficacy in patients with recurrent or metastatic disease is extremely poor. Recently-developed immunotherapy is frequently used in various cancers with high malignancy, such as leukemia, melanoma and non-small-cell lung cancer, and achieves promising clinical outcomes. Immunotherapy has been also investigated in CRC, but the outcome is so disappointed in majority of patients, except the PD-1 inhibitor achieved excellent result in CRC with DNA mismatch repair system deficiency. In this review, the authors will mainly introduce the immunophenotype of different subtype of CRC and summarize current advances of clinical trials for CRC immunotherapy. The article will also discuss the reasons for the low efficacy of immunotherapeutic approaches in CRC and provide several potential directions for the future development of CRC immunotherapy.