The Immunomechanical Checkpoint PYK2 Governs Monocyte-to-Macrophage Differentiation in Pancreatic Cancer
This study identifies PYK2 as an immunomechanical checkpoint that drives monocyte-to-macrophage differentiation in PDAC via PIEZO1/integrin-mediated mechanical cues. Targeted deletion of Ptk2b (PYK2) reshapes the PDAC microenvironment and enhances the efficacy of anti-PD-1 immunotherapy, suggesting PYK2 as a promising therapeutic target to overcome immunotherapy resistance.
Authors
- Wenyan Xie (ORCID: https://orcid.org/0000-0001-6898-3216)
- Bi‐Sen Ding (ORCID: https://orcid.org/0000-0001-9578-3738)
- Panpan Ma (ORCID: https://orcid.org/0009-0007-0911-1080)
- Nengwen Ke (ORCID: https://orcid.org/0000-0002-7135-2244)
- Yun-Hua Liu (ORCID: https://orcid.org/0000-0002-2631-795X)
- Hao Kong (ORCID: https://orcid.org/0000-0002-8683-5580)
- Xiangji Wu (ORCID: https://orcid.org/0009-0005-0526-8414)
- Qiang Wei (ORCID: https://orcid.org/0000-0001-5194-8262)
- Hubing Shi (ORCID: https://orcid.org/0000-0002-2926-3440)
- Qingxin Yang (ORCID: https://orcid.org/0000-0002-9685-6553)
- Yuan Wang (ORCID: https://orcid.org/0000-0002-6324-6134)
- Lu Chen (ORCID: https://orcid.org/0000-0002-1083-9729)
- Lang Chen (ORCID: https://orcid.org/0000-0002-3527-4381)
- Xin Yu (ORCID: https://orcid.org/0000-0001-9768-0695)
- Hong Jiang (ORCID: https://orcid.org/0000-0001-9481-9807)
- Jie Yang (ORCID: https://orcid.org/0000-0001-9352-162X)
- Xiuqin Feng
- Ping Wang (ORCID: https://orcid.org/0009-0009-4040-1144)
Institutions
- Sichuan University (CN)
- West China Hospital of Sichuan University (CN)
- Ingenierie des Materiaux polymeres (FR)
- Second Affiliated Hospital of Zhejiang University (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2025-05-08
- DOI
- https://doi.org/10.1158/2159-8290.cd-24-1712
- Citations
- 17
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 19.57