CD3⁺CD56⁺ natural killer T cell infiltration is increased in cervical cancer and negatively correlated with tumour progression

Abstract

This study investigated the phenotype and function of natural killer T (NKT) cells infiltrating cervical cancer tissues, in an attempt to understand the regulation of NKT cells by cervical cancer cells. Forty-two patients with cervical cancer were included. Flow cytometry was used to analyze the percentage of NKT cells in tumour tissues and its correlation with clinical staging and lymphatic metastasis. The expression of surface receptor and effector molecules on infiltrating NKT cells was determined. The changes of the phenotype, subtype and cytotoxicity of NKT cells were investigated. The regulation of NKT cells by cervical cancer cells was investigated by coculture with HeLa or SiHa cells. The effect of TGF-b1 on NKT activity regulated by cervical cancer cells was studied. The results showed that the infiltration of NKT cells in cervical cancer tissues was significantly higher than that in tumour-adjacent tissues, and the degree of infiltration was negatively correlated with the progression of the disease. The activity and killing effect of infiltrating NKT were inhibited in cervical cancer tissues, leading to increase of CD4 þ NKT cells and decrease of CD8 À CD4 À NKT cells. The activity of NKT cells was down-regulated by co-culture with cervical cancer cells, but subtypes of NKT cells were not altered. Cervical cancer cells inhibited the function of NKT cells by secreting TGF-b1. The study demonstrates that the infiltration of NKT cells in cervical cancer tissues is increased significantly and negatively correlated with tumour progression.

TIME Is Ticking for Cervical Cancer

“…Thus, increased circulating TIM-3 expression of T cells and galectin-9 in patients with CC is associated with poor CC prognosis. In addition, increased TIM-3 expression in T regs via galectin-9 interaction increases the immunosuppressive function (IL-10 and TGF-β release) in patients with CC [212,213]. Notably, the systemic galectin-9 level is independent of the local CC TME.…”

“…For example, CD3 + CD56 + NK cell infiltration increases at early CC stages, which decreases as cancer progresses to advanced stages due to higher TGF-β1 in the tumor. TGF-β1 inhibits natural-killer group 2D (NKG2D), CD16, and Ki67 receptor function [213]. The decreased NK cell number in CC TIME is associated with HLA-I downregulation, potentially due to upregulated immunosuppressive cytokines, including IL-10, IL-13, and TGF-β [214], which inhibit NK-cell function.…”

Chasing Uterine Cancer with NK Cell-Based Immunotherapies

“…Larger tumors have fewer NK cells than less advanced tumors [138] (Figure 3A), suggesting that NK cell-targeted therapies in gynecological cancers could have the most significant impact when implemented early. The unique immunological functions of NK cells make them ideal targets for cancer therapy and could prove pivotal to improving treatment.…”