TY - JOUR
T1 - Immune-checkpoint profiles for T cells in bronchoalveolar lavage fluid of patients with immune-checkpoint inhibitor-related interstitial lung disease
AU - Suzuki, Kunihiro
AU - Yanagihara, Toyoshi
AU - Matsumoto, Koichiro
AU - Kusaba, Hitoshi
AU - Yamauchi, Takuji
AU - Ikematsu, Yuki
AU - Tanaka, Kentaro
AU - Otsubo, Kohei
AU - Inoue, Hiroyuki
AU - Yoneshima, Yasuto
AU - Iwama, Eiji
AU - Arimura-Omori, Masako
AU - Harada, Eiji
AU - Hamada, Naoki
AU - Okamoto, Isamu
AU - Nakanishi, Yoichi
N1 - Funding Information:
This research was supported by Daiwa Securities Health Foundation (grant no. 2809 to T. Yanagihara), the QR Program of Kyushu University (grant no. 28332 to T. Yanagihara) and Kyowa Hakko Kirin (T. Yanagihara). We thank Prof. Miyuki Azuma (Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan) for providing us a human PD-L1-expressing mouse fibroblast cell line (MIT1).
Publisher Copyright:
© The Japanese Society for Immunology. 2020. All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
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U2 - 10.1093/intimm/dxaa022
DO - 10.1093/intimm/dxaa022
M3 - Article
C2 - 32253426
AN - SCOPUS:85088847114
SN - 0953-8178
VL - 32
SP - 547
EP - 557
JO - International immunology
JF - International immunology
IS - 8
ER -
