Pinpointing the tumor-specific T-cells via TCR clusters

  1. Mikhail M Goncharov
  2. Ekaterina A Bryushkova
  3. Nikita I Sharaev
  4. Valeria D Skatova
  5. Anastasiya M Baryshnikova
  6. George V Sharonov
  7. Vadim Karnaukhov
  8. Maria T Vakhitova
  9. Igor V Samoylenko
  10. Lev V Demidov
  11. Sergey Lukyanov
  12. Dmitriy M Chudakov  Is a corresponding author
  13. Ekaterina O Serebrovskaya
  1. Skolkovo Institute of Science and Technology, Russian Federation
  2. Pirogov Russian National Research Medical University, Russian Federation
  3. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Federation
  4. NN Blokhin Russian Cancer Research Center, Russian Federation

Abstract

Adoptive T 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 lyzed 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.

Data availability

TCR repertoires have been deposited on:https://figshare.com/projects/Pinpointing_the_tumor-specific_T-cells_via_TCR_clusters/125284

Article and author information

Author details

  1. Mikhail M Goncharov

    Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  2. Ekaterina A Bryushkova

    Pirogov Russian National Research Medical University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  3. Nikita I Sharaev

    Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  4. Valeria D Skatova

    Pirogov Russian National Research Medical University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  5. Anastasiya M Baryshnikova

    Genomics of Adaptive Immunity Department, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  6. George V Sharonov

    Pirogov Russian National Research Medical University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  7. Vadim Karnaukhov

    Center of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  8. Maria T Vakhitova

    Pirogov Russian National Research Medical University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  9. Igor V Samoylenko

    Oncodermatology Department, NN Blokhin Russian Cancer Research Center, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  10. Lev V Demidov

    Oncodermatology Department, NN Blokhin Russian Cancer Research Center, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  11. Sergey Lukyanov

    Pirogov Russian National Research Medical University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.
  12. Dmitriy M Chudakov

    Department of genomics of adaptive immunity, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation
    For correspondence
    chudakovdm@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0430-790X
  13. Ekaterina O Serebrovskaya

    Pirogov Russian National Research Medical University, Moscow, Russian Federation
    Competing interests
    The authors declare that no competing interests exist.

Funding

Ministry of Science and Higher Education of the Russian Federation (075-15-2020-807)

  • Dmitriy M Chudakov

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: All clinical samples were acquired from the N.N. Blokhin National Medical Research Center of Oncology in accordance with protocol MoleMed-0921, approved by the ethical committee on 30 Jan 2020. All patients involved in the study were diagnosed with metastatic melanoma and signed an informed consent prior to collection of their biomaterial.

Copyright

© 2022, Goncharov et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Mikhail M Goncharov
  2. Ekaterina A Bryushkova
  3. Nikita I Sharaev
  4. Valeria D Skatova
  5. Anastasiya M Baryshnikova
  6. George V Sharonov
  7. Vadim Karnaukhov
  8. Maria T Vakhitova
  9. Igor V Samoylenko
  10. Lev V Demidov
  11. Sergey Lukyanov
  12. Dmitriy M Chudakov
  13. Ekaterina O Serebrovskaya
(2022)
Pinpointing the tumor-specific T-cells via TCR clusters
eLife 11:e77274.
https://doi.org/10.7554/eLife.77274

Share this article

https://doi.org/10.7554/eLife.77274

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