TLR7/8 signaling activation enhances the potency of human pluripotent stem cell-derived eosinophils in cancer immunotherapy for solid tumors

• DOI: 10.1186/s40164-025-00613-y
• Publication Date: 2025-03-01T06:44:22Z
• Authors: Sheng Zhu; Zhengyang Zhou; Ruixin Gu; Zixin Zhao; Yingfeng Zhang; Yudi Miao; Qi Lei; Tianxing Liu; Guokai Wang; Chenyi Dai; Yi Huo; Jinghao You; Lejun Lv; Cheng Li; Ming Yin; Chengyan Wang; Hongkui Deng
• Keywords: Infiltration (HVAC); Cancer Immunotherapy

Abstract Background Efficient tumor T-cell infiltration is crucial for the effectiveness of T-cell-based therapies against solid tumors. Eosinophils play roles in recruiting T cells Our group has previously generated induced eosinophils (iEOs) from human pluripotent stem and exhibited synergistic efficacy with CAR-T inhibition. However, administrated might influx into inflammatory lungs, posing a potential safety risk. Mitigating concern enhancing promising development direction further application eosinophils. Methods We developed new approach to generate enhanced potency chemically reprogrammed (hCiPSCs) Toll-like receptor (TLR) 7/8 signaling agonist R848. Results R848-activated iEOs (R-iEOs) showed significantly decreased inflamed indicating lower risk causing airway disorders. Furthermore, these R-iEOs had anti-tumor functions, preferably accumulated at sites, increased infiltration. The combination suppressed growth mice. Moreover, chemo-trafficking R-iEOs, which may contribute lung recruitment cells. Conclusion study provides novel alleviate concerns associated while increasing This finding offers prospective strategy incorporating improve CAR-T-cell immunotherapy tumors future. Graphical