肿瘤浸润性 CD8(+) T 细胞中 N-糖基化缺陷损害 IFN-γ介导的效应功能

T cell-mediated antitumor immunity is modulated, in part, by N-glycosylation.

However, the interplay between N-glycosylation and the loss of effector function in exhausted T cells has not yet been fully investigated.

Here, we delineated the impact of N-glycosylation on the exhaustion of tumor-infiltrating lymphocytes in a murine colon adenocarcinoma model, focusing on the IFN-γ-mediated immune response.

We found that exhausted CD8 + T cells downregulated the oligosaccharyltransferase complex, which is indispensable for N-glycan transfer. Concordant N-glycosylation deficiency in tumor-infiltrating lymphocytes leads to loss of antitumor immunity. Complementing the oligosaccharyltransferase complex restored IFN-γ production and alleviated CD8 + T cell exhaustion, resulting in reduced tumor growth.

Thus, aberrant glycosylation induced in the tumor microenvironment incapacitates effector CD8 + T cells.

Our findings provide insights into CD8 + T cell exhaustion by incorporating N-glycosylation to understand the characteristic loss of IFN-γ, opening new opportunities to amend the glycosylation status in cancer immunotherapies.