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
Affiliations
Mikhail M Goncharov
Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation; Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
Ekaterina A Bryushkova
Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation; Department of Molecular Biology, Moscow State University, Moscow, Russian Federation; Pirogov Russian National Research Medical University, Moscow, Russian Federation
Nikita I Sharaev
Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation
Valeria D Skatova
Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation; Pirogov Russian National Research Medical University, Moscow, Russian Federation
Anastasiya M Baryshnikova
Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation; Pirogov Russian National Research Medical University, Moscow, Russian Federation
George V Sharonov
Pirogov Russian National Research Medical University, Moscow, Russian Federation; Laboratory of Genomics of Antitumor Adaptive Immunity, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation
Vadim Karnaukhov
Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation; Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
Maria T Vakhitova
Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation; Department of Molecular Biology, Moscow State University, Moscow, Russian Federation
Igor V Samoylenko
Oncodermatology Department, NN Blokhin Russian Cancer Research Center, Moscow, Russian Federation
Lev V Demidov
Oncodermatology Department, NN Blokhin Russian Cancer Research Center, Moscow, Russian Federation
Sergey Lukyanov
Pirogov Russian National Research Medical University, Moscow, Russian Federation
Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation; Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation; Pirogov Russian National Research Medical University, Moscow, Russian Federation
Ekaterina O Serebrovskaya
Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation; Pirogov Russian National Research Medical University, Moscow, Russian Federation; Laboratory of Genomics of Antitumor Adaptive Immunity, Privolzhsky Research Medical University, Nizhny Novgorod, Russian Federation
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.
