肿瘤免疫微环境在肿瘤常规治疗效应中的作用

机体免疫系统能识别和杀伤恶变的细胞,从而清除肿瘤细胞或控制其生长.在机体免疫选择压力下,肿瘤细胞可以依靠自身的高突变特性,逃避免疫监视,逐步建立起免疫抑制微环境,以抵抗和抑制机体抗肿瘤免疫反应,从而能够突破限制而持续扩增,最终发展成为临床可见的肿瘤.目前肿瘤治疗的策略主要是着眼于直接抑制肿瘤细胞增殖以及杀伤和清除肿瘤细胞,然而越来越多的研究结果表明,常规治疗导致的肿瘤细胞免疫原性死亡,可以激活先天性免疫信号通路,诱发机体内在的抗肿瘤免疫反应,在肿瘤治疗效应中起着关键作用,尤其对防止残存肿瘤细胞的复发具有非常重要的意义.本文概述肿瘤发生、发展和常规治疗过程中,机体抗肿瘤免疫反应与肿瘤免疫抑制微环境的细胞和分子机制,重点讨论两者在肿瘤常规治疗效应中的作用,解析以肿瘤免疫微环境为靶点的治疗策略,讨论该策略对提高目前肿瘤常规治疗疗效和发展新的肿瘤治疗方案的积极意义.

Effects of tumor immune microenvironment on conventional cancer therapies

The immune system can eliminate malignant cells or prevent tumor growth by recognizing and destroying malignant cells. Under the strong selective pressure from the host immune system, malignant cells can rapidly acquire new phenotypes through high somatic mutations to evade immune surveillance. The selected tumor cell variants make use of all kinds of immunosuppressive mechanisms to establish an immunosuppressive microenvironment to resist and suppress anti-tumor immune response, allowing the tumors expend and become clinically detectable. The current tumor therapies mainly focus on the direct inhibition of tumor cell proliferation, as well as the killing and elimination of tumor cells. However, the growing evidence suggests that the conventional tumor therapies can elicit specific cellular responses that render tumor-cell death immunogenic, which may activate the innate immune signaling pathways and then induce the intrinsic anti-tumor immune responses. This potential mechanism plays a key role in the therapeutic effects of the conventional anticancer treatments, especially in preventing the recurrence of residual tumor cells. Here, we intend to demonstrate the molecular and cellular mechanisms of the anti-tumor immune responses and the immunosuppressive tumor microenvironment in the process of tumor development and the conventional anticancer treatments, especially focusing on their effects on the therapeutic effects of the conventional anticancer treatments. We also attempt to explore the rational therapeutic strategies targeting the components of tumor immune microenvironment, which may shed light on the improvement of the current conventional anticancer therapies and the development of new anticancer treatments.