作者：陈鸿1,2，杨少华2，洪春虹2，董功航3

单位：1.广州医科大学 研究生院，广东 广州 510000；2.中山大学附属第七医院（深圳） 消化医学中心，广东 深圳 518000；3.深圳市中西医结合医院 普外科，广东 深圳 518000

Authors:  Chen Hong1,2，Yang Shaohua2, Hong Chunhong2, Dong Gonghang3

Unit:  1.Graduate School of Guangzhou Medical University, Guangzhou 510000, Guangdong, China；2.Digestive Medical Center, The seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518000, Guangdong, China；3.General Surgery, Shenzhen Traditional Chinese and Western Medicine Hospital, Shenzhen 518000, Guangdong, China

摘要：

免疫检查点抑制剂的出现,增加了许多实体肿瘤的治疗选择。尽管在黑素瘤和肺癌的治疗中效果良好,但大多数转移性结直肠癌患者无法从免疫治疗中获益。免疫检查点抑制剂在错配修复功能缺失转移性结直肠癌患者中明确有显著和持久的临床反应,即使在既往多线治疗失败的群体中也是如此。然而,这种临床获益仅限于小部分肿瘤患者,约占转移性结直肠癌的4%。事实上，抗程序性死亡受体1(programmed cell death protein 1, PD-1)单抗对错配修复功能缺失转移性结直肠癌患者是无效的。迫切需要新颖的治疗策略使这些肿瘤具有免疫应答。破坏肿瘤的疗法(化学疗法,放射疗法和靶向疗法),从而释放肿瘤抗原,是免疫检查点抑制和其他疗法相结合的最直接的策略。这些标准疗法远没有像曾经担心的那样削弱免疫反应,反而还可以增强免疫应答。

关键词：免疫检查点抑制; 转移性结直肠癌; 微卫星不稳定; 微卫星稳定; 错配修复功能缺失; 毒性

Abstract：

The advent of immune checkpoint inhibitors has increased the treatment options for many solid tumors. Despite good results in the treatment of melanoma and lung cancer, most patients with metastatic colorectal cancer do not benefit from immunotherapy. Immune checkpoint inhibitors clearly have a significant and long-lasting clinical response in patients with dMMR mCRC, even in groups that have failed previous multiline treatments. However, this clinical benefit is limited to a small proportion of cancer patients, accounting for approximately 4% of mCRC. In fact, anti-PD1 mAb is not effective in patients with pMMR mCRC. Novel therapeutic strategies are urgently needed to make these tumors immune. The destructive tumor therapy (chemotherapy, radiotherapy and targeted therapy), for releasing tumor antigens, is the most direct strategy which combines checkpoint inhibitors with other treatments. Instead of weakening the immune response as once feared, these standard therapies can enhance the immune response.

Key Words:  Immune checkpoint inhibitors; Metastatic colorectal cancer; Microsatellite instability high; Microsatellite stability; DNA mismatch repair deficiency; Toxicity