Detection of identical T cell clones in peritumoral pleural effusion and pneumonitis lesions in a cancer patient during immune-checkpoint blockade
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Kentaro Tanaka1,*, Toyoshi Yanagihara1,*, Yuki Ikematsu1, Hiroyuki Inoue1, Keiichi Ota1, Eiji Kashiwagi2, Kunihiro Suzuki1, Naoki Hamada1, Ario Takeuchi2, Katsunori Tatsugami2, Masatoshi Eto2, Kayo Ijichi3, Yoshinao Oda3, Kohei Otsubo1, Yasuto Yoneshima1, Eiji Iwama1, Yoichi Nakanishi1 and Isamu Okamoto1
1Research Institute for Diseases of The Chest, Graduate School of Medical Sciences, Kyushu University, Higashu-Ku, Fukuoka 812-8582, Japan
2Department of Urology, Graduate School of Medical Sciences, Kyushu University, Higashu-Ku, Fukuoka 812-8582, Japan
3Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Higashu-Ku, Fukuoka 812-8582, Japan
*These authors have contributed equally to this work
Isamu Okamoto, email: [email protected]
Keywords: immune-related adverse event; immune-checkpoint inhibitor; bronchoalveolar lavage fluid; next-generation sequencing; complementarity-determining region
Received: April 05, 2018 Accepted: June 22, 2018 Published: July 17, 2018
Although immune-related adverse events (irAEs) of treatment with immune-checkpoint 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 drug-activated 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.
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