Reduced Siglec-7 expression on NK cells predicts NK cell dysfunction in primary hepatocellular carcinoma

Major histocompatibility complex class I (MHC-I)-dependent inhibitory receptors on natural killer (NK) cells have been found to contribute to NK cell dysfunction in hepatocellular carcinoma (HCC). However, the roles of MHC-I-independent inhibitory receptors on NK cells in HCC remain poorly defined. In this study, we analyzed the expression of the MHC-I-independent inhibitory receptors sialic acid-binding immunoglobulin-like lectin (Siglec)-7 and Siglec-9 on NK cells by analyzing the peripheral blood of 35 HCC patients and 63 healthy donors. We observed that HCC patients had lower frequencies and total numbers of NK cells in the peripheral blood. Importantly, both the expression levels of Siglec-7 on NK cells and the frequencies of Siglec-7⁺ NK cells were significantly reduced in HCC patients, which was accompanied by a decrease in activating receptor and an increase in inhibitory receptor expression on NK cells. Moreover, Siglec-7⁺ NK cells expressed higher levels of activating receptors and displayed stronger effector functions, compared with Siglec-7^- NK cells. Our findings demonstrate for the first time that reduced Siglec-7 expression predicts NK cell dysfunction in HCC patients, suggesting that Siglec-7 may be a potential marker of functional NK cell subset in HCC patients.