Tertiary lymphoid structure and decreased CD8+ T cell infiltration in minimally invasive adenocarcinoma
Jin Wang,
Dongbo Jiang,
Xiaoqi Zheng,
Wang Li,
Tian Zhao,
Di Wang,
Huansha Yu,
Dongqing Sun,
Ziyi Li,
Jian Zhang,
Zhe Zhang,
Likun Hou,
Gening Jiang,
Ke Fei,
Fan Zhang,
Kun Yang,
Peng Zhang
Affiliations
Jin Wang
Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China
Dongbo Jiang
Department of Immunology, School of Basic Medicine, Air-Force Medical University (Fourth Military Medical University), Xi'an, China
Xiaoqi Zheng
Department of Mathematics, Shanghai Normal University, Shanghai, China
Wang Li
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Life Sciences and Technology, Shanghai, China
Tian Zhao
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Life Sciences and Technology, Shanghai, China
Di Wang
Tissue Bank, Department of Pathology, Experimental Animal Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
Huansha Yu
Tissue Bank, Department of Pathology, Experimental Animal Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
Dongqing Sun
Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China
Ziyi Li
Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China
Jian Zhang
Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China
Zhe Zhang
Department of Gynecologic Oncology, Chinese PLA General Hospital, Beijing, China
Likun Hou
Tissue Bank, Department of Pathology, Experimental Animal Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
Gening Jiang
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
Ke Fei
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
Fan Zhang
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Life Sciences and Technology, Shanghai, China; Corresponding author
Kun Yang
Department of Immunology, School of Basic Medicine, Air-Force Medical University (Fourth Military Medical University), Xi'an, China; Corresponding author
Peng Zhang
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; Corresponding author
Summary: Knowledge of the tumor microenvironment (TME) in patients with early lung cancer, especially in comparison with the matched adjacent tissues, remains lacking. To characterize TME of early-stage lung adenocarcinoma, we performed RNA-seq profiling on 58 pairs of minimally invasive adenocarcinoma (MIA) tumors and matched adjacent normal tissues. MIA tumors exhibited an adaptive TME characterized by high CD4+ T cell infiltration, high B-cell activation, and low CD8+ T cell infiltration. The high expression of markers for B cells, activated CD4+ T cells, and follicular helper T (Tfh) cells in bulk MIA samples and three independent single-cell RNA-seq datasets implied tertiary lymphoid structures (TLS) formation. Multiplex immunohistochemistry staining validated TLS formation and revealed an enrichment of follicular regulatory T cells (Tfr) in TLS follicles, which may explain the lower CD8+ T cell infiltration and attenuated anti-tumor immunity in MIA. Our study demonstrates how integrating transcriptome and pathology characterize TME and elucidate potential mechanisms of tumor immune evasion.
