Pinpointing the tumor-specific T-cells via TCR clusters
- Skolkovo Institute of Science and Technology, Russian Federation
- Pirogov Russian National Research Medical University, Russian Federation
- Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Federation
- 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
Dmitriy M Chudakov
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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Pinpointing the tumor-specific T-cells via TCR clusters
eLife 11:e77274.
https://doi.org/10.7554/eLife.77274
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