机构：[1]Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, P. R. China四川省人民医院[2]Sichuan Cancer Hospital & Institute， Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610047, P R. China四川省肿瘤医院[3]Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, P. R. China四川省人民医院[4]Division of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610047, P. R. China四川省肿瘤医院[5]Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, P. R China[6]Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, Sichuan, 611731, P. R. China[7]Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, P. R. China[8]School of Medicine, University of Electronic Science and Technology of Chengdu, Sichuan, 611731, P. R. China四川省人民医院[9]Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of Chengdu, Sichuan, 610047, P. R. China四川省人民医院四川省肿瘤医院[10]0Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, P. R. China[11]Center of Growth, Metabolism, and Aging, Key Laboratory of BioResource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, 610064, P. R. China[12]GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P. R. China,华中科技大学同济医学院附属同济医院
Neoadjuvant chemoimmunotherapy (NACI) has shown promise in the treatment of resectable esophageal squamous cell carcinoma (ESCC). The microbiomes of patients can impact therapy response, and previous studies have demonstrated that intestinal microbiota influences cancer immunotherapy by activating gut immunity. Here, we investigated the effects of intratumoral microbiota on the response of ESCC patients to NACI. Intra-tumoral microbiota signatures of β-diversity were disparate and predicted the treatment efficiency of NACI. The enrichment of Streptococcus positively correlated with GrzB+ and CD8+ T cell infiltration in tumor tissues. The abundance of Streptococcus could predict prolonged disease-free survival in ESCC. Single-cell RNA sequencing (scRNA-seq) demonstrated that responders displayed a higher proportion of CD8+ effector memory T cells but a lower proportion of CD4+ Treg cells. Mice that underwent fecal microbial transplantation (FMT) or intestinal colonization with Streptococcus from responders showed enrichment of Streptococcus in tumor tissues, elevated tumor-infiltrating CD8+ T cells, and a favorable response to anti-PD-1 treatment. Collectively, this study suggests that intratumoral Streptococcus signatures could predict NACI response and sheds light on the potential clinical utility of intratumoral microbiota for cancer immunotherapy.
基金：
We want to thank all the members of Prof. Xu’s lab who continued to provide kind help and suggestions. This work was supported by the National Natural Science Foundation of China (No. 92259102; No. 81873048).
第一作者机构：[1]Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, P. R. China[2]Sichuan Cancer Hospital & Institute， Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610047, P R. China[3]Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, P. R. China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, P. R. China[2]Sichuan Cancer Hospital & Institute， Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610047, P R. China[3]Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, P. R. China[9]Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of Chengdu, Sichuan, 610047, P. R. China[12]GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P. R. China,[*1]Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, P. R. China[*2]Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P. R. China[*3]Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, 610047, P. R. China
推荐引用方式(GB/T 7714)：
Hong Wu,Xuefeng Leng,Qianshi Liu,et al.Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma[J].CANCER RESEARCH.2023,83(18):3131-3144.doi:10.1158/0008-5472.CAN-22-2593.
APA：
Hong Wu,Xuefeng Leng,Qianshi Liu,Tianqin Mao,Tao Jiang...&Chuan Xu.(2023).Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma.CANCER RESEARCH,83,(18)
MLA：
Hong Wu,et al."Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma".CANCER RESEARCH 83..18(2023):3131-3144
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