PT - JOURNAL ARTICLE AU - HITOMI KAJIKAWA AU - MICHINARI HIRATA AU - MIYA HARUNA AU - AZUMI UEYAMA AU - KATSUTOSHI HIROSE AU - ATSUNARI KAWASHIMA AU - KOTA IWAHORI AU - KAZUHIDE MATSUNAGA AU - SATORU TOYOSAWA AU - NARIKAZU UZAWA AU - HISASHI WADA TI - Tumor-infiltrating ICOS<sup>+</sup> Effector Regulatory T-Cells in Oral Squamous Cell Carcinoma as a Promising Biomarker for Prognosis and ‘Hot’ Tumor AID - 10.21873/anticanres.15717 DP - 2022 May 01 TA - Anticancer Research PG - 2383--2393 VI - 42 IP - 5 4099 - http://ar.iiarjournals.org/content/42/5/2383.short 4100 - http://ar.iiarjournals.org/content/42/5/2383.full SO - Anticancer Res2022 May 01; 42 AB - 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 &lt;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.