%0 Journal Article
%T T cell-inflamed phenotype and increased Foxp3 expression in infiltrating T-cells of mismatch-repair deficient endometrial cancers
%J -
%D 2018
%R https://doi.org/10.1038/s41379-018-0172-x
%X Mismatch repair-deficient endometrial cancers have a high somatic mutation burden, suggesting that patients with these tumors may benefit from immunotherapy. Elucidating the immune suppressive mechanisms of mismatch repair-deficient endometrial cancers is fundamental to developing future immune-based interventions. This study aimed to determine the immune cell populations associated with mismatch repair-deficient endometrial cancers, especially focusing on targetable regulatory pathways of the immune response. A total of 76 endometrial cancer hysterectomy specimens were evaluated for tumor-infiltrating immune cells by immunohistochemistry. Immune specific markers were used to evaluate each specimen for the number of CD8£¿+£¿cytotoxic T lymphocytes, forkhead-box P3 (FoxP3)£¿+£¿regulatory T cells, CD68£¿+£¿tumor-associated macrophages, as well as programmed death-1 (PD-1)£¿+£¿immune cells, and the percentage of programmed death ligand-1 (PD-L1)£¿+£¿immune cells. Mismatch repair-deficient tumors exhibited a significantly higher number of CD8£¿+£¿cytotoxic T lymphocytes (p£¿=£¿0.0006), FoxP3£¿+£¿regulatory T cells (p£¿=£¿0.0003), PD-1£¿+£¿immune cells (p£¿=£¿0.0069), and a higher percentage of PD-L1£¿+£¿immune cells (p£¿=£¿0.0007) occupying the tumor compared to mismatch repair-proficient endometrial cancers. There was no significant difference in CD68£¿+£¿tumor-associated macrophages infiltration between the two groups. Endometrial cancers with tumor PD-L1 expression also showed significantly increased infiltration of CD8£¿+£¿cytotoxic T lymphocytes (p£¿=£¿0.0002), FoxP3£¿+£¿regulatory T cells (p£¿=£¿0.0003), PD-1£¿+£¿immune cells (p£¿<£¿0.0001), and PD-L1£¿+£¿immune cells (p£¿<£¿0.0001). Endometrial cancers showing mismatch repair-deficiency and PD-L1 expression in tumor cells exhibit a prominent T cell-inflamed phenotype. More importantly, the increased number of FoxP3£¿+£¿regulatory T cells in mismatch repair-deficient endometrial cancers suggests that combination therapy by targeting both regulatory T cells and immune checkpoints may be warranted to improve clinical efficacy
%U https://www.nature.com/articles/s41379-018-0172-x