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作者：SCI天天读
SCI
10 April 2024
Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy
（IF: nature immunology, 30.5）
Chen JH, Nieman LT, Spurrell M, Jorgji V, Elmelech L, Richieri P, Xu KH, Madhu R, Parikh M, Zamora I, Mehta A, Nabel CS, Freeman SS, Pirl JD, Lu C, Meador CB, Barth JL, Sakhi M, Tang AL, Sarkizova S, Price C, Fernandez NF, Emanuel G, He J, Van Raay K, Reeves JW, Yizhak K, Hofree M, Shih A, Sade-Feldman M, Boland GM, Pelka K, Aryee MJ, Mino-Kenudson M, Gainor JF, Korsunsky I, Hacohen N. Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy. Nat Immunol. 2024 Mar 19.
The organization of immune cells in human tumors is not well understood. Immunogenic tumors harbor spatially localized multicellular ‘immunity hubs’ defined by expression of the T cell-attracting chemokines CXCL10/ CXCL11 and abundant T cells. Here, we examined immunity hubs in human pre-immunotherapy lung cancer specimens and found an association with beneficial response to PD-1 blockade. Critically, we discovered the stem-immunity hub, a subtype of immunity hub strongly associated with favorable PD-1-blockade outcome. This hub is distinct from mature tertiary lymphoid structures and is enriched for stem-like TCF7+ PD-1+ CD8+ T cells, activated CCR7+ LAMP3+ dendritic cells and CCL19+ fibroblasts as well as chemokines that organize these cells. Within the stem-immunity hub, we find preferential interactions between CXCL10+ macrophages and TCF7− CD8+ T cells as well as between mature regulatory dendritic cells and TCF7+ CD4+ and regulatory T cells. These results provide a picture of the spatial organization of the human intratumoral immune response and its relevance to patient immunotherapy outcomes.
人类肿瘤中免疫细胞的组织结构尚不清楚。免疫原性肿瘤含有空间定位的多细胞“免疫中枢”，由吸引T细胞的趋化因子CXCL10/CXCL11和丰富的T细胞的表达定义。在这里，我们检测了人类接受免疫治疗前肺癌标本中的免疫中枢，发现它与对PD-1阻断剂的积极反应有关。关键的是，我们发现了一种与PD-1阻断剂有利结果强烈相关的免疫中枢的亚型，即干细胞-免疫中枢。该中枢与成熟的第三淋巴结构不同，富含干细胞样TCF7+ PD-1+ CD8+ T细胞、激活的CCR7+ LAMP3+树突细胞和CCL19+成纤维细胞以及将这些细胞组织在一起的趋化因子。在干细胞-免疫中枢内，我们发现CXCL10+巨噬细胞与TCF7- CD8+ T细胞之间以及成熟的调节性树突细胞与TCF7+ CD4+和调节性T细胞之间存在优先的相互作用。这些结果提供了人类肿瘤内免疫反应的空间组织图像及其与患者免疫治疗结果的相关性。
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