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 journalArticlepeer-review

13 Citations (Scopus)

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

All Science Journal Classification (ASJC) codes

  • Oncology

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