Reactivation of dormant anti-tumor immunity - a clinical perspective of therapeutic immune checkpoint modulation.
Reactivation of dormant anti-tumor immunity - a clinical perspective of therapeutic immune checkpoint modulation.
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休眠抗肿瘤免疫的重新激活——治疗性免疫检查点调节的临床视角。
DOI：
10.1186/s12964-016-0155-9
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发表时间：
2017-01-19
期刊：
影响因子：
--
通讯作者：
Pleyer L
中科院分区：
文献类型：
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作者：
Greil R;Hutterer E;Hartmann TN;Pleyer L
为了促进其生长，癌细胞必须抵抗免疫监视并编辑免疫反应。癌症免疫编辑的特征在于原发性肿瘤和转移性小生境的微环境中的细胞组成和炎性细胞因子谱的根本变化，肿瘤细胞与免疫系统之间的相互作用日益复杂。最近的数据表明，遗传不稳定性和免疫编辑不一定是完全不同的过程。增加的突变负荷可能与肿瘤细胞表达的多个新表位相关，从而增加了免疫系统识别和对抗这些细胞的机会。与此同时，免疫系统越来越受到这个过程的抑制和耗尽。因此，免疫检查点调节可能在遗传高度改变且通常极其不利的癌症类型中最成功。此外，免疫系统识别的表位优先由乘客基因突变编码的事实打开了小分子与修饰T细胞活化或耗竭的抗体同时靶向癌症特异性信号传导途径的协同作用的窗口。这篇综述涵盖了目前对免疫学基础的理解的一些方面，这些免疫学基础是了解癌症治疗中迅速发展的治疗努力所必需的，取得了临床成就，并提出了一些迫切的问题，为这一领域的转化研究。
In favor of their outgrowth, cancer cells must resist immune surveillance and edit the immune response. Cancer immunoediting is characterized by fundamental changes in the cellular composition and the inflammatory cytokine profiles in the microenvironment of the primary tumor and metastatic niches, with an ever increasing complexity of interactions between tumor cells and the immune system. Recent data suggest that genetic instability and immunoediting are not necessarily disparate processes. Increasing mutational load may be associated with multiple neoepitopes expressed by the tumor cells and thus increased chances for the immune system to recognize and combat these cells. At the same time the immune system is more and more suppressed and exhausted by this process. Consequently, immune checkpoint modulation may have the potential to be most successful in genetically highly altered and usually extremely unfavorable types of cancer. Moreover, the fact that epitopes recognized by the immune system are preferentially encoded by passenger gene mutations opens windows of synergy in targeting cancer-specific signaling pathways by small molecules simultaneously with antibodies modifying T-cell activation or exhaustion. This review covers some aspects of the current understanding of the immunological basis necessary to understand the rapidly developing therapeutic endeavours in cancer treatment, the clinical achievements made, and raises some burning questions for translational research in this field.