A comprehensive profile of TCF1^(+)progenitor and TCF1−terminally exhausted PD-1^(+)CD8^(+)T cells in head and neck squamous cell carcinoma:implications for prognosis and immunotherapy
A comprehensive profile of TCF1+ progenitor and TCF1- terminally exhausted PD-1+CD8+ T cells in head and neck squamous cell carcinoma:implications for prognosis and immunotherapy作者机构:Hospital of StomatologyGuanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-Sen UniversityGuangzhouChina Hospital of StomatologyKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceSchool of StomatologyZhejiang University School of MedicineHangzhouChina Department of Oral and Maxillofacial SurgeryFirst Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina
出 版 物:《International Journal of Oral Science》 (国际口腔科学杂志(英文版))
年 卷 期:2022年第14卷第1期
页 面:91-99页
核心收录:
学科分类:1003[医学-口腔医学] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金:supported by the National Natural Science Foundations of China (Nos. 81972532, 81991500, 82101017, 81902778, and 81500864) Guangdong Basic and Applied Basic Research Foundation (2020A1515110741)
主 题:PD1 progenitor squamous
摘 要:The heterogeneity of exhausted T cells(Tex)is a critical determinant of immune checkpoint blockade therapy ***,few studies have explored exhausted T cell subpopulations in human *** the present study,we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer(HNSCC)by multiplex immunohistochemistry(mIHC)to investigate two subsets of Tex,CD8+PD1+TCF1+progenitor exhausted T cells(TCF1+Texprog)and CD8+PD1+TCF1−terminally exhausted T cells(TCF1−Texterm).Moreover,fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells(Tregs)in the tumor immune microenvironment(TIME).mIHC and flow cytometry analysis showed that TCF1−Texterm represented a greater proportion of CD8+PD1+Tex than TCF1+Texprog in most ***1+Texprog produced abundant TNFα,while TCF1−Texterm expressed higher levels of CD103,TIM-3,CTLA-4,and ***1−Texterm exhibited a polyfunctional TNFα+GZMB+IFNγ+phenotype;and were associated with better overall survival and recurrence-free *** results also indicated that larger proportions of TCF1−Texterm were accompanied by an increase in the proportion of ***,it was concluded that TCF1−Texterm was the major CD8+PD1+Tex subset in the HNSCC TIME and that these cells favor patient survival.A high proportion of TCF1−Texterm was associated with greater Treg abundance.