Spitzer Matthew H, Carmi Yaron, Reticker-Flynn Nathan E, Kwek Serena S, Madhireddy Deepthi, Martins Maria M, Gherardini Pier Federico, Prestwood Tyler R, Chabon Jonathan, Bendall Sean C, Fong Lawrence, Nolan Garry P, Engleman Edgar G
Department of Pathology, Stanford University, Stanford, CA 94305, USA; Baxter Lab in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Pathology, The Sackler School of Medicine, Tel-Aviv University, Ramat Aviv 69978, Israel.
Cell. 2017 Jan 26;168(3):487-502.e15. doi: 10.1016/j.cell.2016.12.022. Epub 2017 Jan 19.
Immune responses involve coordination across cell types and tissues. However, studies in cancer immunotherapy have focused heavily on local immune responses in the tumor microenvironment. To investigate immune activity more broadly, we performed an organism-wide study in genetically engineered cancer models using mass cytometry. We analyzed immune responses in several tissues after immunotherapy by developing intuitive models for visualizing single-cell data with statistical inference. Immune activation was evident in the tumor and systemically shortly after effective therapy was administered. However, during tumor rejection, only peripheral immune cells sustained their proliferation. This systemic response was coordinated across tissues and required for tumor eradication in several immunotherapy models. An emergent population of peripheral CD4 T cells conferred protection against new tumors and was significantly expanded in patients responding to immunotherapy. These studies demonstrate the critical impact of systemic immune responses that drive tumor rejection.
免疫反应涉及不同细胞类型和组织之间的协调。然而，癌症免疫治疗的研究主要集中在肿瘤微环境中的局部免疫反应。为了更广泛地研究免疫活性，我们使用质谱流式细胞术在基因工程癌症模型中进行了一项全生物体研究。通过开发直观的模型，利用统计推断来可视化单细胞数据，我们分析了免疫治疗后多个组织中的免疫反应。在有效治疗给药后不久，肿瘤和全身的免疫激活都很明显。然而，在肿瘤排斥过程中，只有外周免疫细胞持续增殖。这种全身反应在不同组织之间是协调的，并且在几种免疫治疗模型中是根除肿瘤所必需的。外周CD4 T细胞的一个新兴群体赋予了对新肿瘤的保护作用，并且在对免疫治疗有反应的患者中显著扩增。这些研究证明了驱动肿瘤排斥的全身免疫反应的关键影响。
