Ms4a7 expression in cDC1s determines cross-presentation and antitumor immunity
Conventional type 1 dendritic cells (cDC1s) capture antigens in peripheral tissues and migrate to draining lymph nodes (dLNs) to prime antigen-specific CD8<sup>+</sup> T cells. How tumor antigens are processed to activate CD8<sup>+</sup> 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 <i>Ms4a7</i><sup>-/-</sup> mice showed normal cDC1 development and turnover, they failed to prime antigen-specific CD8<sup>+</sup> T cells following infection or tumor development. In human cancers, <i>MS4A7</i> 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<sup>+</sup> T cell responses.
Authors
- Xiaohong Zhao (ORCID: https://orcid.org/0000-0003-3270-9076)
- Peng Wei (ORCID: https://orcid.org/0000-0002-1519-6478)
- Birui Pan (ORCID: https://orcid.org/0000-0003-4814-3716)
- Qiuyan Lan (ORCID: https://orcid.org/0000-0003-0984-6259)
- Yongzhen Chen (ORCID: https://orcid.org/0000-0002-6114-1267)
- Lei Qin (ORCID: https://orcid.org/0000-0002-9084-2601)
- Ruifeng Li (ORCID: https://orcid.org/0000-0001-6433-7719)
- Kun Wei (ORCID: https://orcid.org/0000-0002-3520-4658)
- Xue Bai (ORCID: https://orcid.org/0000-0002-9059-3078)
- Bowen Yuan (ORCID: https://orcid.org/0009-0009-0424-6378)
- Ling Ni (ORCID: https://orcid.org/0000-0003-1569-882X)
- Zixuan Zhao (ORCID: https://orcid.org/0000-0001-7460-0074)
- Qinli Sun (ORCID: https://orcid.org/0000-0002-1220-3388)
- Wenbo Hu (ORCID: https://orcid.org/0000-0002-6683-6367)
- Chen Dong (ORCID: https://orcid.org/0000-0002-0084-9130)
- Tian Xie (ORCID: https://orcid.org/0009-0003-7759-2032)
- Bowen Xie (ORCID: https://orcid.org/0000-0003-2476-0357)
- Xuan Zhong (ORCID: https://orcid.org/0009-0000-1258-4363)
- Lei Yuan
Institutions
- Central South University (CN)
- Westlake University (CN)
- Third Xiangya Hospital (CN)
- Center for Life Sciences (CN)
- Tsinghua University (CN)
Publication Details
- Journal
- Science
- Published
- 2025-11-13
- DOI
- https://doi.org/10.1126/science.ady5362
- Citations
- 1
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 0.80