肿瘤化疗联合免疫治疗 从理论基础到临床实践

Combining chemotherapy with immunotherapy:from bench to bedside

在过去的几十年里,化疗是肿瘤内科治疗的基石。尽管化疗疗效显著,但维持病情稳定时间不持久。随着对肿瘤免疫学研究的不断深入,近年来肿瘤免疫治疗再次成为热点。与化疗相比,免疫治疗疗效相对缓和,但更为持久。越来越多的研究表明化疗除了对肿瘤细胞的直接杀伤作用,亦可以增加肿瘤细胞的免疫原性,抑制负性免疫信号,改变肿瘤免疫微环境,从而发挥免疫增强作用,为化疗和免疫治疗的联合应用奠定了理论基础。本文根据已知的肿瘤免疫反应机理和近期发现的化疗免疫调节机制,阐述化疗联合免疫治疗的理论基础,并进一步探讨现有的关于联合治疗的基础和临床研究,从而为后续研究指明方向。

Chemotherapy has been the cornerstone of cancer treatment for decades. However, albeit remarkable, the response to chemotherapy is generally short-lived. With deepened understanding of cancer immunology, resurgence was recently witnessed in the field of cancer immunotherapy. Unlike chemotherapy, immunotherapy induces a relatively mild but stable response. Accumulating evi- dence reveals that apart from chemotherapy＇s direct cytotoxic activity, chemotherapy exerts immune-potentiating effects by increas- ing the immunogenicity of tumor cells or by disrupting the tumor-induced immunosuppression and altering the immune microenviron- ment. The latter mechanism serves as the basis for the combined use of chemotherapy and immunotherapy. In this review, we exam- ine the rationale for combinatoriai therapy in accordance with the current understanding on tumor immunity and newly discovered im- mune-based chemotherapeutic mechanisms. We further discuss the available preclinical and clinical studies on the combination of chemotherapy and immunotherapy for cancer treatment. We aim to provide a framework for further research.