Detection of identical T cell clones in peritumoral pleural effusion and pneumonitis lesions in a cancer patient during immune-checkpoint blockade

Kentaro Tanaka, Toyoshi Yanagihara, Yuki Ikematsu, Hiroyuki Inoue, keiichi ota, Eiji Kashiwagi, Kunihiro Suzuki, Naoki Hamada, ario takeuchi, Katsunori Tatsugami, Masatoshi Eto, Kayo Ijichi, Yoshinao Oda, Kohei Otsubo, Yasuto Yoneshima, Eiji Iwama, Yoichi Nakanishi, Isamu Okamoto

Research output: Contribution to journalArticle

Abstract

Although immune-related adverse events (irAEs) of treatment with immunecheckpoint inhibitors may be due to cellular immunity mediated by T lymphocytes, their pathogenesis has remained unknown. Here we collected bronchoalveolar lavage fluid (BALF) from a cancer patient with nivolumab-induced pneumonitis and isolated mononuclear cells for next-generation sequencing of the complementarity-determining region of the T cell receptor (TCR) β chain. Mononuclear cells in peritumoral pleural effusion isolated from the patient were similarly analyzed, and the results obtained for the two specimens were compared. A substantial number of TCRβ clones in BALF were also identified among lymphocytes in the peritumoral pleural effusion. Such a correlation was not apparent between TCRβ clones in BALF and those in peripheral blood. Moreover, many tumor-associated clones with a read frequency of =0.10% were also present in BALF. Our data suggest that irAEs might be induced by drugactivated lymphocytes originating from tumor tissue. Deep sequencing will thus be indispensable for investigations of the immune-based pathogenesis of, and the development of optimal treatments for, irAEs.

Original languageEnglish
Pages (from-to)30587-30593
Number of pages7
JournalOncotarget
Volume9
Issue number55
DOIs
Publication statusPublished - Jul 17 2018

Fingerprint

Bronchoalveolar Lavage Fluid
Pleural Effusion
Pneumonia
Clone Cells
T-Cell Antigen Receptor
T-Lymphocytes
Neoplasms
Lymphocytes
Complementarity Determining Regions
High-Throughput Nucleotide Sequencing
Cellular Immunity
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

@article{2eebda43422344eb9c4f2c218d8c1388,
title = "Detection of identical T cell clones in peritumoral pleural effusion and pneumonitis lesions in a cancer patient during immune-checkpoint blockade",
abstract = "Although immune-related adverse events (irAEs) of treatment with immunecheckpoint inhibitors may be due to cellular immunity mediated by T lymphocytes, their pathogenesis has remained unknown. Here we collected bronchoalveolar lavage fluid (BALF) from a cancer patient with nivolumab-induced pneumonitis and isolated mononuclear cells for next-generation sequencing of the complementarity-determining region of the T cell receptor (TCR) β chain. Mononuclear cells in peritumoral pleural effusion isolated from the patient were similarly analyzed, and the results obtained for the two specimens were compared. A substantial number of TCRβ clones in BALF were also identified among lymphocytes in the peritumoral pleural effusion. Such a correlation was not apparent between TCRβ clones in BALF and those in peripheral blood. Moreover, many tumor-associated clones with a read frequency of =0.10{\%} were also present in BALF. Our data suggest that irAEs might be induced by drugactivated lymphocytes originating from tumor tissue. Deep sequencing will thus be indispensable for investigations of the immune-based pathogenesis of, and the development of optimal treatments for, irAEs.",
author = "Kentaro Tanaka and Toyoshi Yanagihara and Yuki Ikematsu and Hiroyuki Inoue and keiichi ota and Eiji Kashiwagi and Kunihiro Suzuki and Naoki Hamada and ario takeuchi and Katsunori Tatsugami and Masatoshi Eto and Kayo Ijichi and Yoshinao Oda and Kohei Otsubo and Yasuto Yoneshima and Eiji Iwama and Yoichi Nakanishi and Isamu Okamoto",
year = "2018",
month = "7",
day = "17",
doi = "10.18632/oncotarget.25743",
language = "English",
volume = "9",
pages = "30587--30593",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "55",

}

TY - JOUR

T1 - Detection of identical T cell clones in peritumoral pleural effusion and pneumonitis lesions in a cancer patient during immune-checkpoint blockade

AU - Tanaka, Kentaro

AU - Yanagihara, Toyoshi

AU - Ikematsu, Yuki

AU - Inoue, Hiroyuki

AU - ota, keiichi

AU - Kashiwagi, Eiji

AU - Suzuki, Kunihiro

AU - Hamada, Naoki

AU - takeuchi, ario

AU - Tatsugami, Katsunori

AU - Eto, Masatoshi

AU - Ijichi, Kayo

AU - Oda, Yoshinao

AU - Otsubo, Kohei

AU - Yoneshima, Yasuto

AU - Iwama, Eiji

AU - Nakanishi, Yoichi

AU - Okamoto, Isamu

PY - 2018/7/17

Y1 - 2018/7/17

N2 - Although immune-related adverse events (irAEs) of treatment with immunecheckpoint inhibitors may be due to cellular immunity mediated by T lymphocytes, their pathogenesis has remained unknown. Here we collected bronchoalveolar lavage fluid (BALF) from a cancer patient with nivolumab-induced pneumonitis and isolated mononuclear cells for next-generation sequencing of the complementarity-determining region of the T cell receptor (TCR) β chain. Mononuclear cells in peritumoral pleural effusion isolated from the patient were similarly analyzed, and the results obtained for the two specimens were compared. A substantial number of TCRβ clones in BALF were also identified among lymphocytes in the peritumoral pleural effusion. Such a correlation was not apparent between TCRβ clones in BALF and those in peripheral blood. Moreover, many tumor-associated clones with a read frequency of =0.10% were also present in BALF. Our data suggest that irAEs might be induced by drugactivated lymphocytes originating from tumor tissue. Deep sequencing will thus be indispensable for investigations of the immune-based pathogenesis of, and the development of optimal treatments for, irAEs.

AB - Although immune-related adverse events (irAEs) of treatment with immunecheckpoint inhibitors may be due to cellular immunity mediated by T lymphocytes, their pathogenesis has remained unknown. Here we collected bronchoalveolar lavage fluid (BALF) from a cancer patient with nivolumab-induced pneumonitis and isolated mononuclear cells for next-generation sequencing of the complementarity-determining region of the T cell receptor (TCR) β chain. Mononuclear cells in peritumoral pleural effusion isolated from the patient were similarly analyzed, and the results obtained for the two specimens were compared. A substantial number of TCRβ clones in BALF were also identified among lymphocytes in the peritumoral pleural effusion. Such a correlation was not apparent between TCRβ clones in BALF and those in peripheral blood. Moreover, many tumor-associated clones with a read frequency of =0.10% were also present in BALF. Our data suggest that irAEs might be induced by drugactivated lymphocytes originating from tumor tissue. Deep sequencing will thus be indispensable for investigations of the immune-based pathogenesis of, and the development of optimal treatments for, irAEs.

UR - http://www.scopus.com/inward/record.url?scp=85050157801&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050157801&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.25743

DO - 10.18632/oncotarget.25743

M3 - Article

VL - 9

SP - 30587

EP - 30593

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 55

ER -