RNA-Seq-Based TCR Profiling Reveals Persistently Increased Intratumoral Clonality in Responders to Anti-PD-1 Therapy.

Abstract

Substantial effort is being invested in the search for peripheral or intratumoral T cell receptor (TCR) repertoire features that could predict the response to immunotherapy. Here we demonstrate the utility of MiXCR software for TCR and immunoglobulin repertoire extraction from RNA-Seq data obtained from sorted tumor-infiltrating T and B cells. We use this approach to extract TCR repertoires from RNA-Seq data obtained from sorted tumor-infiltrating CD4+ and CD8+ T cells in an HKP1 (KrasG12Dp53-/-) syngeneic mouse model of lung cancer after anti-PD-1 treatment. For both subsets, we demonstrate decreased TCR diversity in response to therapy. At a later time point, repertoire diversity is restored in progressing disease but remains decreased in responders to therapy in both CD4+ and CD8+ subsets. These observations complement previous studies and suggest that stably increased intratumoral CD4+ and CD8+ T cell clonality after anti-PD-1/PD-L1 therapy could serve as a predictor of long-term response.

• Authors: Ekaterina A Zhigalova, Anna I Izosimova, Diana V Yuzhakova, Lilia N Volchkova, Irina A Shagina, Maria A Turchaninova, Ekaterina O Serebrovskaya, Elena V Zagaynova, Dmitriy M Chudakov, George V Sharonov
• Journal: Frontiers in oncology (Front Oncol) Vol. 10 Pg. 385 ( 2020) ISSN: 2234-943X [Print] Switzerland
• PMID: 32411589 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Zhigalova, Izosimova, Yuzhakova, Volchkova, Shagina, Turchaninova, Serebrovskaya, Zagaynova, Chudakov and Sharonov.