美国麻省理工学院和哈佛大学布罗德研究所Nir Hacohen和Aviv Regev团队合作发现人类结直肠癌中空间组织的多细胞免疫中枢。这一研究成果于2021年8月26日发表在国际顶尖学术期刊《细胞》上。

为了理解控制不同反应的规律，他们转录分析了来自 28 个错配修复缺陷 (MMRp)和 34 个错配修复缺陷 (MMRd)个体的结直肠肿瘤和邻近正常组织的 371,223 个细胞。对 88 个细胞亚群及其 204 个相关基因表达程序的分析揭示了跨肿瘤的广泛转录和空间重塑。为了发现相互作用的恶性细胞和免疫细胞的中枢，他们确定了不同细胞类型中的表达程序，这些细胞类型在受影响个体的肿瘤共变，并使用空间分析来定位协调程序。

他们在肿瘤-管腔界面处发现了一个与组织损伤相关的髓样细胞吸引中枢和肿瘤内富含 MMRd 的免疫中枢，其中激活的 T 细胞与表达 T 细胞吸引趋化因子的恶性细胞和髓样细胞一起。通过识别相互作用的细胞程序，他们揭示了空间组织的免疫恶性细胞网络的潜在逻辑。

据悉，对对癌症的免疫反应是高度可变的，MMRd肿瘤比错配修复缺陷 MMRp肿瘤表现出更多的抗肿瘤免疫力。

附：英文原文

Title: Spatially organized multicellular immune hubs in human colorectal cancer

Author: Karin Pelka, Matan Hofree, Jonathan H. Chen, Siranush Sarkizova, Joshua D. Pirl, Vjola Jorgji, Alborz Bejnood, Danielle Dionne, William H. Ge, Katherine H. Xu, Sherry X. Chao, Daniel R. Zollinger, David J. Lieb, Jason W. Reeves, Christopher A. Fuhrman, Margaret L. Hoang, Toni Delorey, Lan T. Nguyen, Julia Waldman, Max Klapholz, Isaac Wakiro, Ofir Cohen, Julian Albers, Christopher S. Smillie, Michael S. Cuoco, Jingyi Wu, Mei-ju Su, Jason Yeung, Brinda Vijaykumar, Angela M. Magnuson, Natasha Asinovski, Tabea Moll, Max N. Goder-Reiser, Anise S. Applebaum, Lauren K. Brais, Laura K. DelloStritto, Sarah L. Denning, Susannah T. Phillips, Emma K. Hill, Julia K. Meehan, Dennie T. Frederick, Tatyana Sharova, Abhay Kanodia, Ellen Z. Todres, Judit Jané-Valbuena, Moshe Biton, Benjamin Izar, Conner D. Lambden, Thomas E. Clancy, Ronald Bleday, Nelya Melnitchouk, Jennifer Irani, Hiroko Kunitake, David L. Berger, Amitabh Srivastava, Jason L. Hornick, Shuji Ogino, Asaf Rotem, Sébastien Vigneau, Bruce E. Johnson, Ryan B. Corcoran, Arlene H. Sharpe, Vijay K. Kuchroo, Kimmie Ng, Marios Giannakis, Linda T. Nieman, Genevieve M. Boland

Issue&Volume: 2021-08-26

Abstract: Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd individuals. Analysis of 88 cell subsets and their 204 associated gene expression programs revealed extensive transcriptional and spatial remodeling across tumors. To discover hubs of interacting malignant and immune cells, we identified expression programs in different cell types that co-varied across tumors from affected individuals and used spatial profiling to localize coordinated programs. We discovered a myeloid cell-attracting hub at the tumor-luminal interface associated with tissue damage and an MMRd-enriched immune hub within the tumor, with activated T cells together with malignant and myeloid cells expressing T cell-attracting chemokines. By identifying interacting cellular programs, we reveal the logic underlying spatially organized immune-malignant cell networks.

DOI: 10.1016/j.cell.2021.08.003

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00945-4