Focused on key TME regulators that control cDC1 cross-presentation, Xie et al. found that cDC1-expressed Ms4a7 was critical for effective CD8+ T cell-mediated antitumor immunity in mouse models. Tumor antigen induced Ms4a7 expression and NF-κB activation in cDC1s and tumor dLNs, which was required to cross-prime antigen-specific CD8+ T cells. Ms4a7-/- cDC1s showed reduced migration to dLNs, made less IL-12, IL-18, and IL-27 in the TME, and failed to prime CD8+ T cell activation, resulting in diminished antitumor immunity. In human cancers, Ms4a7 was expressed in a subset of cDC1s, enriched in dLNs, and correlated with patient survival.
Contributed by Katherine Turner
ABSTRACT: Conventional type 1 dendritic cells (cDC1s) capture antigens in peripheral tissues and migrate to draining lymph nodes (dLNs) to prime antigen-specific CD8(+) T cells. How tumor antigens are processed to activate CD8(+) T cell immunity is not well understood. In this work, we show that Ms4a7 is up-regulated in cDC1s after tumor antigen uptake or exposure to exogenous stimuli and is required for their cross-priming ability. Although Ms4a7(-/-) mice showed normal cDC1 development and turnover, they failed to prime antigen-specific CD8(+) T cells following infection or tumor development. In human cancers, MS4A7 was expressed in a subset of cDC1s, preferentially enriched in dLNs, and correlated with patient survival. Our findings suggest a critical role for Ms4a7 in cDC1-mediated cross-presentation and antitumor CD8(+) T cell responses.
Author Info: (1) Westlake University School of Medicine, Hangzhou, Zhejiang, China. Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. Tsinghua-Peking Center
Author Info: (1) Westlake University School of Medicine, Hangzhou, Zhejiang, China. Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China. (2) Department of Pathology, The Third Xiangya Hospital, Central South University, Changsha, China. (3) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (4) Westlake University School of Medicine, Hangzhou, Zhejiang, China. Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (5) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (6) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China. (7) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (8) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (9) Westlake University School of Medicine, Hangzhou, Zhejiang, China. Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (10) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (11) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (12) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (13) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (14) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China. (15) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (16) Westlake University School of Medicine, Hangzhou, Zhejiang, China. (17) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (18) Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China. (19) Westlake University School of Medicine, Hangzhou, Zhejiang, China.
