Immune-checkpoint profiles for T cells in bronchoalveolar lavage fluid of patients with immune-checkpoint inhibitor-related interstitial lung disease

Kunihiro Suzuki, Toyoshi Yanagihara, Koichiro Matsumoto, Hitoshi Kusaba, Takuji Yamauchi, Yuki Ikematsu, Kentaro Tanaka, Kohei Otsubo, Hiroyuki Inoue, Yasuto Yoneshima, Eiji Iwama, Masako Arimura-Omori, Eiji Harada, Naoki Hamada, Isamu Okamoto, Yoichi Nakanishi

Research output: Contribution to journalArticle

Abstract

Immune-checkpoint inhibitors (ICIs) have improved clinical outcomes and are becoming a standard treatment for many cancer types. However, these drugs also induce immune-related adverse events, among which interstitial lung disease (ILD) is potentially fatal. The underlying mechanism of ILD induction by ICIs is largely unknown. With the use of flow cytometry, we determined the expression levels of the immune-checkpoint proteins PD-1, TIM-3, TIGIT, LAG-3 and PD-L1 in T cells of bronchoalveolar lavage fluid (BALF) from patients with ICI-related ILD and compared them with those for patients with sarcoidosis or with ILD related to connective tissue disease or cytotoxic drug use. The proportions of CD8+ T cells positive for both PD-1 and TIM-3 or for TIGIT in BALF were significantly higher for ICI-related ILD patients than for those with other types of ILD. A prominent increase in the proportion of PD-1+PD-L1+ cells among CD8+ T cells was also apparent in BALF of a patient with a fatal case of ICI-related ILD, and the proportion of such cells was positively correlated with the grade of ICI-related ILD. Our data reveal the immune-checkpoint profiles of T cells in ICI-related ILD and may provide mechanistic insight into the development of this adverse event.

Original languageEnglish
Pages (from-to)547-557
Number of pages11
JournalInternational immunology
Volume32
Issue number8
DOIs
Publication statusPublished - Aug 1 2020

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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