NK cell transfer overcomes resistance to PD-(L)1 therapy in aged mice

• DOI: 10.1186/s40164-024-00511-9
• Publication Date: 2024-05-09T08:01:54Z
• Authors: Junlei Hou; Shuanglong Xie; Jianbao Gao; Tao Jiang; Enjian Zhu; Xuezhi Yang; Zheng Jin; Haixia Long; Anmei Zhang; Fei Yang; Lujing Wang; Haoran Zha; Qingzhu Jia; Bo Zhu; Xinxin Wang
• Keywords: Hematology; Cell therapy

Abstract Background Cancer is the leading cause of death among older adults. Although integration immunotherapy has revolutionized therapeutic landscape cancer, complex interactions between age and efficacy remain incompletely defined. Here, we aimed to elucidate relationship aging resistance. Methods Flow cytometry was performed evaluate infiltration immune cells in tumor microenvironment (TME). In vivo T cell proliferation, cytotoxicity migration assays were antitumor capacity antigen-specific CD8 + mice. Real-time quantitative PCR (qPCR) used investigate expression IFN-γ-associated gene natural killer (NK)-associated chemokine. Adoptive NK transfer adopted effects from young mice overcoming resistance aged Results We found that elderly patients with advanced non-small lung cancer (aNSCLC) ≥ 75 years exhibited poorer progression-free survival (PFS), overall (OS) a lower clinical response rate after immunotherapy. Mechanistically, showed significantly reduced compared younger Furthermore, could also suppress activation by inhibiting recruitment CD103 dendritic (DCs). promoted TME remodeling, reversed Conclusion Our findings revealed decreased sensitivity immunotherapy, as well This may be attributed reduction mice, which inhibits DCs its CD86 ultimately leads