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

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 pneumon...

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Detalles Bibliográficos
Autores principales: Tanaka, Kentaro, Yanagihara, Toyoshi, Ikematsu, Yuki, Inoue, Hiroyuki, Ota, Keiichi, Kashiwagi, Eiji, Suzuki, Kunihiro, Hamada, Naoki, Takeuchi, Ario, Tatsugami, Katsunori, Eto, Masatoshi, Ijichi, Kayo, Oda, Yoshinao, Otsubo, Kohei, Yoneshima, Yasuto, Iwama, Eiji, Nakanishi, Yoichi, Okamoto, Isamu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078130/
https://www.ncbi.nlm.nih.gov/pubmed/30093971
http://dx.doi.org/10.18632/oncotarget.25743
Descripción
Sumario: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.