Intratumoral CD103^(+)CD8^(+)T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma
作者机构:Department of Oral and Maxillofacial SurgerySun Yat-sen Memorial Hospital of Sun Yat-sen UniversityGuangdongP.R.China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationGuangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangdongP.R.China Department of Gynecological OncologySun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangdongP.R.China School of StomatologyJilin UniversityJilinP.R.China Stomatology Hospital of Haizhu districtGuangdongP.R.China
出 版 物:《Cancer Communications》 (癌症通讯(英文))
年 卷 期:2023年第43卷第10期
页 面:1143-1163页
核心收录:
学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金:supported by the National Natural Science Foundation of China(82272788,82072990,81903045,and 82072988) China Postdoctoral Science Foundation(2021M703692) Department of Health of Guangdong Province Science Foundation(A2022165 and A2021142) Guangzhou Municipal Science and Technology Project(202201011479) Guangdong Science and Technology Development Fund(2019A1515011867 and 2020A1515010405)
主 题:CD103 CD8 head and neck squamous cell carcinoma neoadjuvant chemoimmunotherapy predictive marker tumor-infiltrating lymphocyte
摘 要:Background Immune cell heterogenicity is known to determine the therapeutic response to cancer *** chemoimmunotherapy(NACI)has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma(HNSCC),but the underlying mechanism behind this clinical response is *** efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical ***,we attempted to identify molecules predicting NACI response in advanced *** We performed combined single-cell RNA sequencing(scRNA-seq)and multiplex immunofluorescence(mIHC)staining with tumor samples derived from NACI-treated HNSCC patients to identify a new tumor-infiltrating cell(TIL)subtype,CD103^(+)CD8^(+)TILs,associated with clinical response,while both in vitro and in vivo assays were carried out to determine its antitumor *** regulatory mechanism of the CD103^(+)CD8^(+)TILs population was examined by performing cell-cell interaction analysis of the scRNA-seq data and spatial analysis of the mIHC *** We established intratumoral CD103^(+)CD8^(+)TILs density as a determinant of NACI efficacy in *** scRNA-seq results indicated that the population of CD103^(+)CD8^(+)TILs was dramatically increased in the responders of NACI-treated HNSCC patients,while mIHC analysis confirmed the correlation between intratumoral CD103^(+)CD8^(+)TILs density and NACI efficacy in HNSCC *** receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to *** assays showed that CD103^(+)CD8^(+)TILs were tumor-reactive T cells,while programmed cell death protein-1(PD-1)blockade enhanced CD103^(+)CD8^(+)TILs cytotoxicity against tumor growth in ***,targeting the triggering receptor expressed on myeloid cells 2-positive(TREM2^(+))macrophages might enhance the population of CD103^(+)CD8^(+)TILs and facilitate antitumor immunity