Targeting VSIG4+ tissue-resident macrophages enhances T cell cytotoxicity and immunotherapy efficacy in cancer by Zikun Ma, Yuzhao Wang,Weikai Wang, ..., Xiangdong Li,Xiaoyu Liang, Zhuowei Liu ISBN 101016/JDEVCEL202504011 instant download

Targeting VSIG4+ tissue-resident macrophages enhances T cell cytotoxicity and immunotherapy efficacy in cancer by Zikun Ma, Yuzhao Wang,Weikai Wang, ..., Xiangdong Li,Xiaoyu Liang, Zhuowei Liu ISBN 101016/JDEVCEL202504011 instant download

SUMMARYTissue-resident macrophage (TRM) is crucial for organ development and homeostasis. However, the role ofTRM-derived tumor-associated macrophage (TAM) subpopulations in cancer remains unclear. Using singlecell RNA sequencing and lineage tracing, we reported a TRM-derived TAM subpopulation, characterized byVSIG4 overexpression in testicular cancer. Macroscopically, such subpopulation was also found in tumorssuch as hepatocellular carcinoma, lung cancer, and glioblastoma. It was associated with poor prognosisand the suppression of CD8+ T-cell-dependent immunity via VSIG4. Notably, VSIG4 promoted immunosuppressive effects through direct or indirect modes, including interacting with receptors on CD8+ T cells orinducing transcription of IL-11 in TAMs. More importantly, MEF2C was identified as a key transcription factorthat maintained VSIG4 expression and determined the biological behaviors of VSIG4+ TAMs. In preclinicalmodels, targeting VSIG4+ TAMs via VSIG4 or MEF2C demonstrated a favorable effect of enhancing the efficacy of immune checkpoint inhibitors.