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

doi:10.1016/j.isci.2023.107732

Immune-active tumor-adjacent tissues are associated with favorable prognosis in stage I lung squamous cell carcinoma

iScience. 2023 Aug 25;26(9):107732. doi: 10.1016/j.isci.2023.107732. eCollection 2023 Sep 15.

Authors

Lisha Ying¹, Chunliu Zhang², Alexandre Reuben³, Yiping Tian⁴, Jiaoyue Jin⁴, Canming Wang⁴, Jing Bai², Xinyuan Liu^{4

5}, Jianfei Fang⁴, Tingting Feng^{1

4}, Chenyang Xu⁴, Rui Zhu⁴, Minran Huang⁴, Yingqi Lyu^{4

6}, Tingting Lu^{4

6}, Xiaodan Pan⁷, Jianjun Zhang^{3

8}, Dan Su⁴

Affiliations

¹ Zhejiang Cancer Institute, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
² Geneplus-Beijing Institute, Beijing, China.
³ Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁴ Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
⁵ The Second Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China.
⁶ Department of Oncology, The First Clinical Medical College of Wenzhou Medical University, Wenzhou, Zhejiang 325015, China.
⁷ Human Tissue Bank, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
⁸ Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract

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.

Keywords: Immunology; Oncology; Transcriptomics.