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

doi:10.1016/j.isci.2022.103883

Tertiary lymphoid structure and decreased CD8⁺ T cell infiltration in minimally invasive adenocarcinoma

iScience. 2022 Feb 9;25(3):103883. doi: 10.1016/j.isci.2022.103883. eCollection 2022 Mar 18.

Authors

Jin Wang¹, Dongbo Jiang², Xiaoqi Zheng³, Wang Li⁴, Tian Zhao⁴, Di Wang⁵, Huansha Yu⁵, Dongqing Sun¹, Ziyi Li¹, Jian Zhang⁶, Zhe Zhang⁷, Likun Hou⁵, Gening Jiang⁸, Ke Fei⁸, Fan Zhang⁴, Kun Yang², Peng Zhang⁸

Affiliations

¹ Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
² Department of Immunology, School of Basic Medicine, Air-Force Medical University (Fourth Military Medical University), Xi'an, China.
³ Department of Mathematics, Shanghai Normal University, Shanghai, China.
⁴ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Life Sciences and Technology, Shanghai, China.
⁵ Tissue Bank, Department of Pathology, Experimental Animal Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
⁶ Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China.
⁷ Department of Gynecologic Oncology, Chinese PLA General Hospital, Beijing, China.
⁸ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

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.

Keywords: Cancer; Components of the immune system; Immunity.