Tumor-infiltrating ICOS Effector Regulatory T-Cells in Oral Squamous Cell Carcinoma as a Promising Biomarker for Prognosis and 'Hot' Tumor.

BACKGROUND

Tumor immunity in the tumor microenvironment is activated in patients with feasible clinical responses to immune checkpoint inhibitors. The immunological profile of tumor-infiltrating lymphocytes (TILs) obtained from patients with oral squamous cell carcinoma (OSCC) was examined in relation to their prognosis.

MATERIALS AND METHODS

Surface antigens, including immune checkpoint molecules, on TILs from 31 patients with primary OSCC were analyzed by flow cytometry. The activation status of TILs was examined through a heatmap analysis and unsupervised clustering classified patients into groups with activated or inactivated TILs. A supervised machine-learning algorithm for single-cell analyses in relation to prognosis was run using the Cluster Identification, Characterization, and Regression (CITRUS) program.

RESULTS

None of surface antigens were related to prognosis. The CITRUS program revealed a relationship between CD45RACD4 CD25 inducible T-cell co-stimulator (ICOS) TILs and recurrence, and also identified a similar fraction significantly specific to the group with activated TILs. The disease-free survival rate for patients with ≥95% ICOS TILs was significantly lower than that for those with <95% ICOS TILs. Furthermore, a review of clinicopathological factors related to prognosis identified the percentage of ICOS TILs to be an independent prognostic factor for patients with OSCC.

CONCLUSION

CD25ICOS regulatory T-cells in TILs have potential as a biomarker for predicting recurrence after surgical treatment and clinical responses to immune checkpoint inhibitors in patients with OSCC.