结直肠癌的免疫治疗

Immunotherapy for Colorectal Cancer

改善结直肠癌(colorectal cancer,CRC)患者的预后具有重要的临床和社会意义。免疫治疗是一种新兴的肿瘤治疗方式,免疫检查点抑制剂已在DNA错配修复缺陷/高微卫星不稳定型CRC的治疗中实现了良好的临床转化,占绝大多数的DNA错配修复完整/微卫星稳定型CRC患者却很难在该疗法中获益。免疫疫苗、过继性细胞疗法等其他免疫疗法的临床研究也在积极推进中,虽然展示了一定的良性结果,但仍面临着难以有效突破肿瘤抑制性微环境等诸多问题而未能获得实质性进展。本文以各种免疫治疗方案相关的临床试验为主线进行综述,以期明确CRC免疫治疗的进展,为更优治疗方案的探索提供依据。

Improving the prognosis of patients with colorectal cancer(CRC)holds important clinical and social significance.Immunotherapy is an emerging therapy approach for cancers,which mainly include immune checkpoint inhibitors(ICI),immune vaccine and adoptive cell therapy.ICI have achieved good clinical translation in treatment of metastatic CRC with deficient DNA mismatch repair/high microsatellite instability(dMMR/MSI-H)status.The application of some ICI,such as PD-1 inhibitors pembrolizumab and nivolumab,in this type patients have been approved by the FDA.In addition,numerous positive results are acquired in clinical trials of neoadjuvant therapy for resectable dMMR/MSI-H CRC.These results greatly bolstered the exploration enthusiasm of CRC immunotherapy.However,the proficient DNA mismatch repair/microsatellite stability(pMMR/MSS)CRC,which accounting for the vast majority in related patients,hardly benefit from ICI therapy.Various combination strategies,mainly including ICI combined with traditional chemotherapy,radiotherapy,or targeted therapy,have been attempted to alter the“cold tumors”microenvironment characteristics of pMMR/MSS CRC in clinical trials,whereas no breakthrough results were reached.Theoretically,tumor vaccines are ideal choice to break down the barrier of insufficient immune infiltration in solid tumors.However,the outcomes of related clinical trials in CRC patents are not satisfactory,and partially due to the weak specificity of the applied tumor-associated antigens.Clinical studies of adoptive cell therapy in CRC are also actively underway.The favorable efficacy of tumor-infiltrating lymphocyte,cytokine-induced killer(CIK)and dendritic cell-CIK in CRC have been confirmed,while the CAR-T and TCR-T therapies need more exploration based on screening more suitable antigens and optimizing engineering design.In this review,we made a summary based on the mainline of clinical studies related to diverse immunotherapies,so as to clarify the progress of CRC immunotherapy and provide bases for exploration of better treatment options.