美国哈佛医学院和麻省理工学院Nir Hacohen，Ilya Korsunsky，Justin F. Gainor和Jonathan H. Chen共同合作，近期取得重要工作进展。他们研究提出，人类肺癌具有与免疫治疗反应相关的空间组织干免疫中枢。相关研究成果2024年3月19日在线发表于《自然—免疫学》杂志上。

据介绍，人类肿瘤中免疫细胞的组织尚不清楚。免疫原性肿瘤具有空间定位的多细胞“免疫中枢”，由T细胞吸引趋化因子CXCL10/CXCL11和大量T细胞的表达定义。

研究人员检测了人类免疫治疗前癌症标本中的免疫中枢，发现其与PD-1阻断的有益反应有关。至关重要的是，研究人员发现了干细胞免疫中枢，这是一种与有利的PD-1阻断结果密切相关的免疫中枢亚型。

该中枢不同于成熟的三级淋巴结构，富含干细胞样TCF7⁺PD-1⁺CD8⁺ T细胞、活化的CCR7⁺ LAMP3⁺树突状细胞和CCL19⁺成纤维细胞以及组织这些细胞的趋化因子。在干细胞免疫中枢中，研究人员发现CXCL10⁺巨噬细胞与TCF7−CD8⁺T细胞之间，以及成熟的调节性树突状细胞与TCF7⁺CD4⁺和调节性T细胞之间的优先相互作用。

总之，这些结果提供了人类肿瘤内免疫反应的空间组织及其与患者免疫治疗结果的相关性。

附：英文原文

Title: Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy

Author: Chen, Jonathan H., Nieman, Linda T., Spurrell, Maxwell, Jorgji, Vjola, Elmelech, Liad, Richieri, Peter, Xu, Katherine H., Madhu, Roopa, Parikh, Milan, Zamora, Izabella, Mehta, Arnav, Nabel, Christopher S., Freeman, Samuel S., Pirl, Joshua D., Lu, Chenyue, Meador, Catherine B., Barth, Jaimie L., Sakhi, Mustafa, Tang, Alexander L., Sarkizova, Siranush, Price, Colles, Fernandez, Nicolas F., Emanuel, George, He, Jiang, Van Raay, Katrina, Reeves, Jason W., Yizhak, Keren, Hofree, Matan, Shih, Angela, Sade-Feldman, Moshe, Boland, Genevieve M., Pelka, Karin, Aryee, Martin J., Mino-Kenudson, Mari, Gainor, Justin F., Korsunsky, Ilya, Hacohen, Nir

Issue&Volume: 2024-03-19

Abstract: 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 TCF7CD8+ 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.

DOI: 10.1038/s41590-024-01792-2

Source: https://www.nature.com/articles/s41590-024-01792-2