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Review
. 2022 May;42(5):2383-2393.
doi: 10.21873/anticanres.15717.

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

Hitomi Kajikawa  1   2 , Michinari Hirata  1   3 , Miya Haruna  1   3 , Azumi Ueyama  1   3 , Katsutoshi Hirose  4 , Atsunari Kawashima  1   5 , Kota Iwahori  1 , Kazuhide Matsunaga  2 , Satoru Toyosawa  4 , Narikazu Uzawa  2 , Hisashi Wada  6
Affiliations
Review

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

Hitomi Kajikawa et al. Anticancer Res. 2022 May.

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.

Keywords: Oral squamous cell carcinoma; flow cytometry; immune checkpoint; regulatory T-lymphocytes; tumor-infiltrating lymphocytes.

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