scRNAseq analysis was performed on matched primary and metastatic tumors, normal tissue, LNs, and PBMCs from treatment-naive patients with CRC (n=17) or HCC (n= 16). Phenotypic alignment of cells across samples enabled the classification of exhausted CD8+ T cells, Tregs, mast cells, 3 types of macrophages (SPP1+, MK167+, and C1QC+) as associated with malignancy. NK cells, NKT cells, DCs and γδ T cells were associated with tissue niche. As revealed by TCR clonotype analyses, both Treg-FOXP3 and effector memory cells circulated from the blood to both primary and metastatic sites – a finding that bolsters the rationale for ACT.
Contributed by Margot O’Toole
ABSTRACT: The tumor microenvironment (TME) is connected to immunotherapy responses, but it remains unclear how cancer cells and host tissues differentially influence the immune composition within TME. Here, we performed single-cell analyses for autologous samples from liver metastasized colorectal cancer to disentangle factors shaping TME. By aligning CD45(+) cells across different tissues, we classified exhausted CD8(+) T cells (Texs) and activated regulatory T cells as M-type, whose phenotypes were associated with the malignancy, while natural killer and mucosal-associated invariant T cells were defined as N-type, whose phenotypes were associated with the niche. T cell receptor sharing between Texs in primary and metastatic tumors implicated the presence of common peripheral non-exhausted precursors. For myeloid cells, a subset of dendritic cells (DC3s) and SPP1(+) macrophages were M-type, and the latter were predominant in liver metastasis, indicating its pro-metastasis role. Our analyses bridge immune phenotypes of primary and metastatic tumors, thereby helping to understand the tumor-specific contexture and identify the pro-metastasis components.
Author Info: (1) BIOPIC, School of Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. (2) BIOPIC
Author Info: (1) BIOPIC, School of Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. (2) BIOPIC, School of Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. (3) Department of Hepatopancreatobiliary Surgery I, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China. (4) Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 10038, China. (5) BIOPIC, School of Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. (6) BIOPIC, School of Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. (7) BIOPIC, School of Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. (8) Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China. (9) Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 10038, China; Ninth School of Clinical Medicine, Peking University, Beijing 10038, China. Electronic address: pengjr@bjsjth.cn. (10) BIOPIC, School of Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address: renxwise@pku.edu.cn. (11) BIOPIC, School of Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, China. Electronic address: zemin@pku.edu.cn.
