Inhibitory receptors for HLA class I as immune checkpoints for natural killer cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy

Abstract

Natural killer (NK) cells mediate potent anti-tumor responses, which makes them attractive targets for immunotherapy. The anti-tumor response of endogenous- or allogeneic NK cells can be enhanced through clinically available monoclonal antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC). NK cell activation is regulated by interaction of inhibitory receptors with classical- and non-classical human leukocyte antigens (HLA) class I molecules. Inhibitory receptors of the killer immunoglobulin-like receptor (KIR) family interact with HLA-A, -B or –C epitopes, while NKG2A interacts with the non-classical HLA-E molecule. Both types of inhibitory interactions may influence the strength of the ADCC response. In the present review, we provide an overview of the effect of inhibitory KIRs and NKG2A on NK cell-mediated ADCC, which highlights the rationale for combination strategies with ADCC triggering antibodies and interference with the NK cell relevant inhibitory immune checkpoints, such as KIR and NKG2A.

Identification and immunological characterization of cuproptosis-related molecular clusters in retinoblastoma

“…Plasma cells in ltrate the tumor site [33], and even a small number of cells can produce large amounts of cytokines and antibodies [34]. These antibodies promote anti-tumor immunity by driving antibody-dependent cytotoxicity (ADCC) and phagocytosis, complement activation, and enhanced antigen presentation by dendritic cells [35]. Tfh cells are required for the survival and differentiation of autoreactive B cells and the production of a large number of pathogenic antibodies [36,37].…”

Contribution of an Asian-prevalent HLA haplotype to the risk of HBV-related hepatocellular carcinoma

“…The mechanisms underlying these observations remain unclear. Previous studies suggest that HLA-class I molecules expressed on tumor cells mediate NK cell suppression 28 . Intriguingly, we observed infrequent LOH of the B*52:01 and C*12:02 alleles (which are associated with increased risk) compared with other class I alleles in HCCs of individuals heterozygous for these alleles (Supplementary Fig.…”

Multiomic single-cell analysis identifies von Willebrand factor and TIM3-expressingBCR-ABL1+CML stem cells

“…VWF was a top LSC-upregulated gene in these comparisons (Figure 4L). Other top differentially regulated genes included HLA-E and CD48 that encode structures of relevance to NK cell recognition 21,22 . At the protein level, TIM3 was significantly upregulated in LSC compared with HSC from both healthy donors and TKI-treated patients (Figure 4M).…”