CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Cellular Tumor Immune Microenvironment of Childhood Solid Cancers: Informing More Effective Immunotherapies.
The Cellular Tumor Immune Microenvironment of Childhood Solid Cancers: Informing More Effective Immunotherapies.
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常见的儿童实体瘤对依赖预先存在的适应性抗肿瘤免疫应答的标准免疫肿瘤药物无反应。过继转移肿瘤抗原特异性T细胞,如CAR基因修饰T细胞,是一种有吸引力的策略,但其疗效有限。越来越多的证据表明,肿瘤微环境中的局部屏障阻止T细胞浸润并阻碍治疗性免疫应答。全面了解肿瘤微环境功能组成部分及其相互作用,可为有效的联合治疗和新型工程化治疗提供信息,推动免疫治疗在儿科患者中充分发挥潜力。本综述总结了当前关于儿童和青少年常见颅外实体癌(如胚胎性肿瘤及骨和软组织肉瘤)中肿瘤微环境的细胞组成及意义的知识,重点关注这些肿瘤中常大量存在的髓系细胞群体。本文介绍了用药理学抗癌剂和选择性拮抗剂(共)靶向免疫抑制性髓系细胞群体的策略,以及旨在利用髓系细胞与抗肿瘤T细胞应答协同作用的新概念。
Common pediatric solid cancers fail to respond to standard immuno-oncology agents relying on preexisting adaptive antitumor immune responses. The adoptive transfer of tumor-antigen specific T cells, such as CAR-gene modified T cells, is an attractive strategy, but its efficacy has been limited. Evidence is accumulating that local barriers in the tumor microenvironment prevent the infiltration of T cells and impede therapeutic immune responses. A thorough understanding of the components of the functional compartment of the tumor microenvironment and their interaction could inform effective combination therapies and novel engineered therapeutics, driving immunotherapy towards its full potential in pediatric patients.
This review summarizes current knowledge on the cellular composition and significance of the tumor microenvironment in common extracranial solid cancers of childhood and adolescence, such as embryonal tumors and bone and soft tissue sarcomas, with a focus on myeloid cell populations that are often present in abundance in these tumors.
Strategies to (co)target immunosuppressive myeloid cell populations with pharmacological anticancer agents and with selective antagonists are presented, as well as novel concepts aiming to employ myeloid cells to cooperate with antitumor T cell responses.
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