Tumor-secreted AGR2 induces dendritic cell dysfunction and impairs immunotherapy efficacy in LKB1-deficient cancer
Our study identifies profound DC dysfunction-characterized by impaired antigen uptake, migration, and naïve CD8<sup>+</sup> T-cell priming-as a key mechanism of immune evasion in LKB1-deficient tumors. This dysfunction is driven by tumor-secreted AGR2, which stabilizes ARG1 in DCs and suppresses CD8<sup>+</sup> T-cell activation. Targeting the AMPKα-FOXA1-AGR2-ARG1 axis or restoring DC competence offers a promising strategy to enhance immunotherapy efficacy in LKB1-deficient subtype.
Authors
- Chengming Liu (ORCID: https://orcid.org/0000-0002-5818-4848)
- Yuxin Yao (ORCID: https://orcid.org/0009-0003-9286-2790)
- Xiaoya Tang (ORCID: https://orcid.org/0000-0002-7826-2049)
- Sufei Zheng
- Nan Sun (ORCID: https://orcid.org/0000-0001-6812-9917)
- Enzhi Yin (ORCID: https://orcid.org/0000-0002-4265-0058)
- Xin‐Feng Wang (ORCID: https://orcid.org/0009-0003-5834-4009)
- Zhanyu Wang (ORCID: https://orcid.org/0000-0001-9187-6419)
- Jie He (ORCID: https://orcid.org/0000-0002-0285-5403)
- Yuejun Luo
Institutions
- Capital Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking University (CN)
- Beijing Jishuitan Hospital (CN)
- National Cancer Center (US)
- National Clinical Research Center for Digestive Diseases (CN)
- Henan Academy of Sciences (CN)
Publication Details
- Journal
- Journal for ImmunoTherapy of Cancer
- Published
- 2025-10-01
- DOI
- https://doi.org/10.1136/jitc-2025-012710
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00