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

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

    Research output: Contribution to journalArticlepeer-review

    6 Citations (Scopus)

    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.

    Original languageEnglish
    Article number385
    JournalFrontiers in Oncology
    Volume10
    DOIs
    Publication statusPublished - 28 Apr 2020

    Keywords

    • anti-PD-1
    • MiXCR
    • RNA-Seq
    • T cell clonality
    • TCR repertoire
    • tumor-infiltrating lymphocytes

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