Impairment of IgG Fc functions promotes tumor progression and suppresses NK cell antitumor actions

• DOI: 10.1038/s42003-022-03931-7
• Publication Date: 2022-09-14T14:03:52Z
• Authors: Xuejun Fan; Zihao Yuan; Yueshui Zhao; Wei Xiong; Hao-Ching Hsiao; Rahmawati Pare; Jianmin Ding; Ahmad Almosa; Kai Sun; Songlin Zhang; Robert E. Jordan; Cheok Song Lee; Zhiqiang An; Ningyan Zhang
• Keywords: 0301 basic medicine; QH301-705.5; Antineoplastic Agents; Article; 3. Good health; Killer Cells, Natural; Mice; 03 medical and health sciences; Immunoglobulin G; Neoplasms; XXXXXX - Unknown; Tumor Microenvironment; Animals; Biology (General); Neoplastic Processes

Abstract Natural killer (NK) cells mediate antibody dependent cytotoxic killing of cancer via cross-linking FcγR on NK with IgG-Fc. Studies have shown that the single-hinge cleaved IgGs (scIgGs) dysfunctional Fc and failed engagement FcγRs immune cells. However, little is known about how scIgGs impact antitumor immunity in tumor microenvironment. In this study, we revealed a significant association progression poor outcomes breast patients ( n = 547). Using multiple mouse models, demonstrated reduced cell activities resulted aggressive progression. We further showed an anti-hinge specific monoclonal (AHA) rescued by providing functional restored activity. These findings point to novel immunotherapeutic strategy enhance for activation anticancer immunity.