Intratumoral CD103^(+)CD8^(+)T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma  

作　　者：Siqi Ren Tianjun Lan Fan Wu Suling Chen Xue Jiang Chuying Huo Zitian Li Shule Xie Donghui Wu Ruixin Wang Yanyan Li Lin Qiu Guoxin Huang Shurui Li Xiaojuan Wang Meifeng Cen Tingting Cai Zhaoyu Lin Jinsong Li Bowen Li 

机构地区：[1]Department of Oral and Maxillofacial Surgery,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangdong,P.R.China [2]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Guangdong-Hong Kong Joint Laboratory for RNA Medicine,Medical Research Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangdong,P.R.China [3]Department of Gynecological Oncology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangdong,P.R.China [4]School of Stomatology,Jilin University,Jilin,P.R.China [5]Stomatology Hospital of Haizhu district,Guangdong,P.R.China

出　　处：《Cancer Communications》2023年第10期1143-1163,共21页癌症通讯（英文）

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).

摘　　要：Background Immune cell heterogenicity is known to determine the therapeutic response to cancer progression.Neoadjuvant 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 unknown.The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses.Here,we attempted to identify molecules predicting NACI response in advanced HNSCC.Methods 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 efficiency.The 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 images.Results We established intratumoral CD103^(+)CD8^(+)TILs density as a determinant of NACI efficacy in cancers.Our 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 patients.Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI.Functional 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 vivo.Mechanistically,targeting the triggering receptor expressed on myeloid cells 2-positive(TREM2^(+))macrophages might enhance the population of CD103^(+)CD8^(+)TILs and facilitate antitumor immunity during NACI treatment.Conclusions Our study hig

关 键 词：CD103 CD8 head and neck squamous cell carcinoma neoadjuvant chemoimmunotherapy predictive marker tumor-infiltrating lymphocyte 

分 类 号：R739.91[医药卫生—肿瘤]