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

• Published in: Oncotarget 2018-07, Vol.9 (55), p.30587-30593
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.25743

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.