Caitlin C. Zebley, Dietmar Zehn, Stephen Gottschalk, Hongbo Chi
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引用次数: 0
Abstract
Recent advances in immunotherapy have affirmed the curative potential of T cell-based approaches for treating relapsed and refractory cancers. However, the therapeutic efficacy is limited in part owing to the ability of cancers to evade immunosurveillance and adapt to immunological pressure. In this Review, we provide a brief overview of cancer-mediated immunosuppressive mechanisms with a specific focus on the repression of the surveillance and effector function of T cells. We discuss CD8+ T cell exhaustion and functional heterogeneity and describe strategies for targeting the molecular checkpoints that restrict T cell differentiation and effector function to bolster immunotherapeutic effects. We also delineate the emerging contributions of the tumor microenvironment to T cell metabolism and conclude by highlighting discovery-based approaches for developing future cellular therapies. Continued exploration of T cell biology and engineering hold great promise for advancing therapeutic interventions for cancer. In this Review, the authors analyze functional and dysfunctional T cell features to make sense of cancer immunotherapy efficacy and how to improve it.
免疫疗法的最新进展证实,以 T 细胞为基础的方法具有治疗复发和难治性癌症的潜力。然而,由于癌症具有逃避免疫监视和适应免疫压力的能力,其疗效受到一定限制。在本综述中,我们将简要概述癌症介导的免疫抑制机制,并特别关注对 T 细胞监控和效应功能的抑制。我们讨论了 CD8+ T 细胞衰竭和功能异质性,并介绍了针对限制 T 细胞分化和效应功能的分子检查点以增强免疫治疗效果的策略。我们还描述了肿瘤微环境对 T 细胞代谢的新贡献,最后强调了开发未来细胞疗法的发现型方法。对 T 细胞生物学和工程学的持续探索为推进癌症治疗干预措施带来了巨大希望。
期刊介绍:
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.