MACC1 facilitates the escape of nasopharyngeal carcinoma cells from killing by natural killer cells

Abstract

This study examined the regulation of phenotype and function of natural killer (NK) cells by nasopharyngeal carcinoma (NPC) cells with metastasis-associated in colon cancer-1 (MACC1) overexpression. Thirty patients with NPC and 20 healthy subjects were included. Peripheral blood (5 mL) was collected, and NK cells were purified using Ficoll and negative separation. NPC HONE1 cells were transfected with pcDNA3.1-MACC1 or negative control plasmids, and culture supernatant was collected for co-culture with NK cells. Flow cytometry was used to determine the expression of activated and inhibitory receptors on the cells. Western blotting was used to determine the expression of proteins. The results showed that the ratio of NK cells in the peripheral blood of NPC patients was elevated, but the activity and tumor-killing effect of NK cells were reduced. MACC1 promoted the escape of HONE1 cells from killing by NK cells. HONE1 with overexpression of MACC1 down-regulated the expression of NKG2D in NK cells, inhibited the proliferation of NK cells and escaped the immune surveillance by NK cells. MACC1 downregulated the expression of NKG2D in NK cells by up-regulating the expression of TGF-b1 in HONE1 cells, thereby inhibiting the activity of NK cells. MACC1 inhibited the cell cycle of NK cells via TGF-b1 pathway. The study demonstrated that MACC1 elevated the expression of TGF-b1 by NPC HONE1 cells, thereby inhibiting NKG2D expression and G1/S transition in NK cells. MACC1 helped NPC HONE1 cells avoid killing by NK cells.

Utilization of four galactans by Bacteroides thetaiotaomicron A4 based on transcriptome

“…The results were presented as mean ± standard deviation and were analyzed using one‐way analysis of variance with SPSS 20.0. Least significant difference method and Dunnett's T3 method were used for the post‐hoc test, in the case of homogeneity and heterogeneity of variance, respectively (Zhao, Liu, Liang, Feng, & Xu, 2019). p < 0.05 was considered statistically significant.…”

The Role of NK Cells in EBV Infection and EBV-Associated NPC

“…Latent protein LMP1 can contribute to NK evasion in several ways. First, LMP1 allows EBV-infected cells to survive despite being co-cultured with p TGF-β1, which is a known NK-inhibiting cytokine [ 112 , 113 , 114 ]. LMP1 does so through the upregulation of inhibitor of differentiation-1 (Id-1), which negates effects of TGF-β1 against NPC [ 115 ].…”

“…Analysis of peripheral blood lymphocytes between NPC patients and healthy individuals revealed no differences in NK cell abundance or percentage based on analysis of CD56 + CD3 - in two studies [ 121 , 122 ]. Another study, however, noted a higher percentage of circulating NK cells in NPC patients compared to healthy controls [ 112 ]. With regards to NK cell phenotypes, one study noted no difference in terms of percentage of NK cells positive for NKG2D (NK activating) and KIR2DL2/DL3 (CD158b) and NK2GA (CD159a) (both NK inhibitory) between NPC and healthy controls [ 122 ].…”

“…In another study, a lower percentage of activated NK cells (NKG2D and Granzyme B positive) was noted in NPC patients, while a higher percentage of NK cells expressing inhibitory ligands (KIR2DL2/KIR3DL3) was seen in NPC patients than healthy controls. These findings indicated poorer functional NK cells in NPC patients than in healthy controls [ 112 ]. The list of relevant NK receptors and ligands reported in NPC is summarized in Table 3 .…”

“…In another study, Zhao and colleagues showed that diminished NKG2D-positive NK population could be induced by overexpression of metastasis-associated colon cancer-1 (MACC1) on NPC [ 112 ]. They showed that the overexpression of MACC1 on NPC cells promoted increased expression of TGF-β1, a potent inhibitor of NK cells, which downregulates NKG2D [ 112 ]. However, the experiments were performed on HONE1 cell line, which was reportedly an NPC cell line contaminated with HeLa cells [ 125 ].…”