CD8(+) T-cell exhaustion in the tumor microenvironment of head and neck squamous cell carcinoma determines poor prognosis

Background: The occurrence of HNSCC is closely related to the immune system. The integration of traditional treatment methods and immunotherapy will be the future development direction of cancer treatment. But immunotherapy also has its limitations: a lot of basic research is going on, but the translation from basic to clinical is still not enough, and there are still few drugs approved for use.This study aimed to explore the clinical significance of the tumor immune microenvironment in HNSCC. Methods: Six clinically obtained postoperative cases were analyzed using multiplex immunohistochemistry (mIHC) to observe the tumor immune microenvironment and analyze infiltrating immune cells. Correlations between infiltrating immune cells from The Cancer Genome Atlas (TCGA) database and clinicopathological features of 510 HNSCC patients were then analyzed. Kaplan-Meier survival analysis was used to detect the relationship between the expression of different immune cells and the prognosis of HNSCC patients, and univariate and multivariate Cox regression analyses were used to analyze the prognostic factors associated with HNSCC patients. We validated the prognostic and predictive accuracy based on the expression of CD8(+) T-cells in an independent group of 510 patients. Results: We detected infiltration of CD8(+) T cells, NK cells, and macrophages in patients with laryngeal squamous cell carcinoma by multiplex immunofluorescence. The infiltration of the three types of immune cells in the tumor stroma was significantly higher than in the tumor parenchyma. Our results also showed the infiltration of CD8(+) T cells was associated with prognosis, and the COX regression model showed CD8(+) T cells were an independent prognostic factor in HNSCC patients. The higher density of infiltrating CD8(+) T cells had the better prognosis. In addition, we developed a nomogram for clinical use that integrated the CD8(+) T-cells-based classifier and three clinicopathological risk factors to predict the prognosis of HNSCC patients. Conclusions: CD8(+) T-cell exhaustion in the tumor microenvironment of HNSCC determines poor prognosis and can be combined with the tumor stage to improve the accuracy of prognosis assessment in HNSCC patients.