The nexus of dynamic T cell states and immune checkpoint blockade therapy in the periphery and tumor microenvironment.
The nexus of dynamic T cell states and immune checkpoint blockade therapy in the periphery and tumor microenvironment.
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DOI：
10.3389/fimmu.2023.1267918
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发表时间：
2023
影响因子：
7.3
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Luo H;Wang W;Mai J;Yin R;Cai X;Li Q
免疫检查点阻断（ICB）疗法，即使用单克隆抗体从CTLA-4、PD-1和PD-L1免疫检查点的抑制作用中重振肿瘤反应性抗原特异性T细胞，彻底改变了现代肿瘤学的治疗前景。然而，只有一部分患者可以从ICB治疗中获益。在过去的十年中，与ICB反应、抗性和预后相关的生物标志物已经受到深入研究。早期的研究集中在肿瘤标本及其驻留微环境的分析。然而，活检在临床实践中可能具有挑战性，并且不能反映ICB治疗期间免疫学参数的动态变化。最近的研究已经使用多组学方法研究了来自外周室的抗原特异性T细胞的概况。通过跟踪肿瘤反应性T细胞受体库的克隆型和多样性，这些研究共同确立了外周血中抗原特异性T细胞的从头引发发生在整个ICB过程中，而ICB之前预先存在的T细胞在不同程度上被耗尽。在这里，我们回顾什么是已知的ICB诱导的T细胞的表型和功能的变化，在癌症患者的肿瘤微环境和外周隔室。更好地了解影响ICB反应的参数将为开发新的诊断和组合治疗策略提供理论基础，以最大限度地提高ICB治疗的临床疗效。
Immune checkpoint blockade (ICB) therapies, that is, using monoclonal antibodies to reinvigorate tumor-reactive, antigen-specific T cells from the inhibitory effects of CTLA-4, PD-1 and PD-L1 immune checkpoints, have revolutionized the therapeutic landscape of modern oncology. However, only a subset of patients can benefit from the ICB therapy. Biomarkers associated with ICB response, resistance and prognosis have been subjected to intensive research in the past decade. Early studies focused on the analysis of tumor specimens and their residing microenvironment. However, biopsies can be challenging to obtain in clinical practice, and do not reflect the dynamic changes of immunological parameters during the ICB therapy. Recent studies have investigated profiles of antigen-specific T cells derived from the peripheral compartment using multi-omics approaches. By tracking the clonotype and diversity of tumor-reactive T cell receptor repertoire, these studies collectively establish that de novo priming of antigen-specific T cells in peripheral blood occurs throughout the course of ICB, whereas preexisting T cells prior to ICB are exhausted to various degrees. Here, we review what is known about ICB-induced T cell phenotypic and functional changes in cancer patients both within the tumor microenvironment and in the peripheral compartment. A better understanding of parameters influencing the response to ICBs will provide rationales for developing novel diagnostics and combinatorial therapeutic strategies to maximize the clinical efficacies of ICB therapies.
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影响因子：
15.9
作者：
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