T cell immunity in interstitial lung disease with non-small cell lung cancer patients

Tomomi Isono; Kota Iwahori; Masahiro Yanagawa; Yoko Yamamoto; Mari Tone; Miya Haruna; Michinari Hirata; Eriko Fukui; Toru Kimura; Takashi Kanou; Naoko Ose; Soichiro Funaki; Yoshito Takeda; Eiichi Morii; Atsushi Kumanogoh; Yasushi Shintani; Hisashi Wada

doi:10.1016/j.lungcan.2023.107278

T cell immunity in interstitial lung disease with non-small cell lung cancer patients

Lung Cancer. 2023 Aug:182:107278. doi: 10.1016/j.lungcan.2023.107278. Epub 2023 Jun 9.

Authors

Tomomi Isono¹, Kota Iwahori², Masahiro Yanagawa³, Yoko Yamamoto¹, Mari Tone⁴, Miya Haruna⁵, Michinari Hirata⁵, Eriko Fukui¹, Toru Kimura¹, Takashi Kanou¹, Naoko Ose¹, Soichiro Funaki¹, Yoshito Takeda⁴, Eiichi Morii⁶, Atsushi Kumanogoh⁷, Yasushi Shintani¹, Hisashi Wada⁸

Affiliations

¹ Department of Thoracic Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
² Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan. Electronic address: iwahori@climm.med.osaka-u.ac.jp.
³ Department of Radiology, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁴ Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁵ Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Biopharmaceutical Research Division, Shionogi & Co., Ltd., Osaka, Japan.
⁶ Department of Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁷ Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan; Center for Infectious Diseases for Education and Research (CiDER), Osaka University, Osaka, Japan; Japan Agency for Medical Research and Development - Core Research for Evolutional Science and Technology (AMED-CREST), Osaka University, Osaka, Japan; Center for Advanced Modalities and DDS (CAMaD), Osaka University, Osaka, Japan.
⁸ Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.

PMID: 37321075
DOI: 10.1016/j.lungcan.2023.107278

Abstract

Objectives: Limited treatment options are available for non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD). The rationale for immunotherapy and its adverse events for NSCLC with ILD remains unclear. In this study, we examined T cell profiles and functions in the lung tissues of NSCLC patients with or without ILD to provide evidence for the potential mechanism of immune checkpoint inhibitor (ICI)-related pneumonitis in NSCLC patients with ILD.

Material and methods: We investigated T cell immunity in the lung tissues of NSCLC patients with ILD to support the application of immunotherapy for these patients. We analyzed T cell profiles and functions in surgically resected lung tissues from NSCLC patients with and without ILD. The T cell profiles of infiltrating cells in lung tissues were analyzed by flow cytometry. T cell functions were measured based on cytokine production by T cells stimulated with phorbol 12-myristate 13-acetate and ionomycin.

Results: The percentages of CD4⁺ T cells expressing immune checkpoint molecules (Tim-3, ICOS, and 4-1BB), CD103⁺CD8⁺ T cells, and regulatory T (Treg) cells were higher in NSCLC patients with than in those without ILD. A functional analysis of T cells in lung tissues indicated that CD103⁺CD8⁺ T cells positively correlated with IFNγ production, whereas Treg cells negatively correlated with IFNγ and TNFα production. Cytokine production by CD4⁺ and CD8⁺ T cells did not significantly differ between NSCLC patients with and without ILD, except for TNFα production by CD4⁺ T cells being lower in the former than in the latter.

Conclusion: In NSCLC patients with ILD stable for surgery, T cells were active participants and balanced in part by Treg cells in lung tissues, suggesting the potential development of ICI-related pneumonitis in NSCLC patients with ILD.

Keywords: Interstitial lung disease; Non-small cell lung cancer; Tumor necrosis factor-α; regulatory T cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
Carcinoma, Non-Small-Cell Lung* / therapy
Humans
Lung Diseases, Interstitial*
Lung Neoplasms* / therapy
Pneumonia*
Retrospective Studies
Tumor Necrosis Factor-alpha

Substances

Tumor Necrosis Factor-alpha