Faculty, Staff and Student Publications
Language
English
Publication Date
9-14-2022
Journal
Communications Biology
DOI
10.1038/s42003-022-03931-7
PMID
36104515
PMCID
PMC9474879
PubMedCentral® Posted Date
9-14-2022
PubMedCentral® Full Text Version
Post-print
Abstract
Natural killer (NK) cells mediate antibody dependent cytotoxic killing of cancer cells via cross-linking FcγR on NK cells with IgG-Fc. Studies have shown that the single-hinge cleaved IgGs (scIgGs) have dysfunctional Fc and failed engagement with FcγRs on immune cells. However, little is known about how scIgGs impact on antitumor immunity in the tumor microenvironment. In this study, we revealed a significant association of tumor scIgGs with tumor progression and poor outcomes of breast cancer patients (n = 547). Using multiple mouse tumor models, we demonstrated that tumor scIgGs reduced NK cell cytotoxic activities and resulted in aggressive tumor progression. We further showed that an anti-hinge specific monoclonal antibody (AHA) rescued the dysfunctional Fc in scIgGs by providing a functional Fc and restored NK cell cytotoxic activity. These findings point to a novel immunotherapeutic strategy to enhance Fc engagement with FcγRs for activation of anticancer immunity.
Keywords
Animals, Antineoplastic Agents, Immunoglobulin G, Killer Cells, Natural, Mice, Neoplasms, Neoplastic Processes, Tumor Microenvironment
Published Open-Access
yes
Recommended Citation
Fan, Xuejun; Yuan, Zihao; Zhao, Yueshui; et al., "Impairment of IgG FC Functions Promotes Tumor Progression and Suppresses Nk Cell Antitumor Actions" (2022). Faculty, Staff and Student Publications. 2823.
https://digitalcommons.library.tmc.edu/uthmed_docs/2823