Abstract
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 CD45RA−CD4+ CD25high 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: CD25highICOS+ 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.
- Oral squamous cell carcinoma
- immune checkpoint
- tumor-infiltrating lymphocytes
- flow cytometry
- regulatory T-lymphocytes
- Received March 1, 2022.
- Revision received March 22, 2022.
- Accepted March 24, 2022.
- Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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