Pinpointing the tumor-specific T cells via TCR clusters

Mikhail M. Goncharov, Ekaterina A. Bryushkova, Nikita I. Sharaev, Valeria D. Skatova, Anastasiya M. Baryshnikova, George V. Sharonov, Vadim Karnaukhov, Maria T. Vakhitova, Igor V. Samoylenko, Lev V. Demidov, Sergey Lukyanov, Dmitriy M. Chudakov, Ekaterina O. Serebrovskaya

Research output: Contribution to journalArticlepeer-review

Abstract

Adoptive cell transfer (ACT) is a promising approach to cancer immunotherapy, but its efficiency fundamentally depends on the extent of tumor-specific T cell enrichment within the graft. This can be estimated via activation with identifiable neoantigens, tumor-associated antigens (TAAs), or living or lysed tumor cells, but these approaches remain laborious, time-consuming, and functionally limited, hampering clinical development of ACT. Here, we demonstrate that homology cluster analysis of T cell receptor (TCR) repertoires efficiently identifies tumor-reactive TCRs allowing to: (1) detect their presence within the pool of tumor-infiltrating lymphocytes (TILs); (2) optimize TIL culturing conditions, with IL-2low/IL-21/anti-PD-1 combination showing increased efficiency; (3) investigate surface marker-based enrichment for tumor-targeting T cells in freshly isolated TILs (enrichment confirmed for CD4+ and CD8+ PD-1+/CD39+ subsets), or re-stimulated TILs (informs on enrichment in 4-1BB-sorted cells). We believe that this approach to the rapid assessment of tumor-specific TCR enrichment should accelerate T cell therapy development.

Original languageEnglish
JournaleLife
Volume11
DOIs
Publication statusPublished - 4 Apr 2022

Keywords

  • cancer immunotherapy
  • human
  • immunology
  • inflammation
  • PD-1+/CD39+
  • T cell receptor repertoires
  • TCR clusters
  • tumor-associated antigens
  • tumor-infiltrating lymphocytes

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