Engineered T cells stimulate dendritic cell recruitment and antigen spreading for potent anti-tumor immunity
Current T cell-based immunotherapeutic strategies show limited success in treating solid tumors due to insufficient dendritic cell (DC) activity, particularly cross-presenting conventional type 1 dendritic cells (cDC1s). DC scarcity and dysfunction hinder T cell expansion and differentiation, greatly limiting anti-tumor responses. In this study, we propose a T cell engineering strategy to enhance interaction with XCR1<sup>+</sup> cDC1s. Adoptively transferred T cells engineered to secrete Flt3L and XCL1 (FX) promote DC trafficking and maturation and improve DC-T cell interaction, while maintaining a pool of TCF1<sup>+</sup>SlamF6<sup>+</sup> stem-like T cells. Importantly, FX-engineered T cells trigger robust antigen spreading and potent endogenous polyclonal T cell response, enabling the recognition and elimination of tumors with heterogeneous antigens and preventing immune escape. The therapeutic efficacy of FX-armed chimeric antigen receptor (CAR)-T cells is further validated in the Flt3KO&hFLT3LG humanized mouse model. This strategy offers a promising avenue for enhancing DC-T cell interactions, paving the way for more effective immunotherapy against solid tumors.
Authors
- Ang Gao (ORCID: https://orcid.org/0000-0002-9513-9114)
- Shiyou Wang (ORCID: https://orcid.org/0000-0003-1901-3920)
- Shidian He (ORCID: https://orcid.org/0000-0002-2743-818X)
- Jing Huang (ORCID: https://orcid.org/0000-0002-0638-4805)
- Hai-Xi Sun
- Kun Tang (ORCID: https://orcid.org/0000-0002-8418-143X)
- Xiaowei Liu (ORCID: https://orcid.org/0000-0002-7479-4865)
- Wen Hui Li (ORCID: https://orcid.org/0000-0002-1848-8855)
- Jingxing Yang (ORCID: https://orcid.org/0000-0002-9390-2104)
- Minmin Ge
- Yabo Zhou (ORCID: https://orcid.org/0000-0002-0519-2158)
- Zhen Xiao (ORCID: https://orcid.org/0000-0002-6132-6149)
- Lin Wang (ORCID: https://orcid.org/0000-0001-7425-7667)
- Chen Wang (ORCID: https://orcid.org/0000-0002-4030-1831)
- Liyuan Zhang (ORCID: https://orcid.org/0000-0002-0290-6776)
- Jiajia Wang (ORCID: https://orcid.org/0000-0002-6581-1774)
- Lianjun Zhang (ORCID: https://orcid.org/0000-0001-9448-7718)
- Yang Yu (ORCID: https://orcid.org/0000-0003-3483-3185)
- Kaili Ma (ORCID: https://orcid.org/0000-0002-5242-3000)
Institutions
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Beijing Institute of Genomics (CN)
- Soochow University (CN)
- Suzhou Institute of Trade & Commerce (CN)
- Suzhou Institute of Systems Medicine (CN)
- Second Affiliated Hospital of Soochow University (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-08-25
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102307
- Citations
- 7
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 7.32
Funders
- National Natural Science Foundation of China
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province