Immune-active tumor-adjacent tissues are associated with favorable prognosis in stage I lung squamous cell carcinoma
Lisha Ying,
Chunliu Zhang,
Alexandre Reuben,
Yiping Tian,
Jiaoyue Jin,
Canming Wang,
Jing Bai,
Xinyuan Liu,
Jianfei Fang,
Tingting Feng,
Chenyang Xu,
Rui Zhu,
Minran Huang,
Yingqi Lyu,
Tingting Lu,
Xiaodan Pan,
Jianjun Zhang,
Dan Su
Affiliations
Lisha Ying
Zhejiang Cancer Institute, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
Chunliu Zhang
Geneplus-Beijing Institute, Beijing, China
Alexandre Reuben
Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Yiping Tian
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
Jiaoyue Jin
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
Canming Wang
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
Jing Bai
Geneplus-Beijing Institute, Beijing, China
Xinyuan Liu
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; The Second Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China
Jianfei Fang
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
Tingting Feng
Zhejiang Cancer Institute, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
Chenyang Xu
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
Rui Zhu
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
Minran Huang
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
Yingqi Lyu
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; Department of Oncology, The First Clinical Medical College of Wenzhou Medical University, Wenzhou, Zhejiang 325015, China
Tingting Lu
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; Department of Oncology, The First Clinical Medical College of Wenzhou Medical University, Wenzhou, Zhejiang 325015, China
Xiaodan Pan
Human Tissue Bank, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
Jianjun Zhang
Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Corresponding author
Dan Su
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; Corresponding author
Summary: The immunogenomic features of tumor-adjacent lungs (TALs) in stage I lung squamous cell carcinoma (LUSC) are not clear. Multiomics analyses of tumor tissues and paired TALs from 59 stage I LUSC patients were performed. Compared to tumors, TALs exhibited a better-preserved immune contexture indicated by upregulation of immune pathways, increased immune infiltration, and higher expression of immune effector molecules. Notably, TALs had no mutations in PTEN and KEAP1, a lower incidence of human leukocyte antigen (HLA) loss and higher expression of HLA class I genes, major histocompatibility complex (MHC) I chaperones, and interferon (IFN)-γ-associated genes. Digital spatial profiling validated the generally higher immune infiltration in TALs and revealed a higher level of immune heterogeneity in LUSC tumors. Importantly, patients with higher immune infiltration in TALs had significantly longer survival, while high immune heterogeneity was associated with inferior patient survival. Our work can be considered in the selection of patients for adjuvant therapy, especially immunotherapy.
