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Contract number
Time span of the project

As of 01.11.2022

Number of staff members
scientific publications
Objects of intellectual property
General information

Name of the project: Clonal composition of tumor-infiltrating T lymphocytes as a forecasting and predictive marker in treatment of oncological illnesses

Goals and objectives

Research directions:

  • Impact of immunotherapy using checkpoint inhibitors on clonal composition of functional subpopulations of T lymphocytes (observed in model mice and clinical samples);
  • Fate of tumor-specific T lymphocytes in development of illness and during response to immunotherapy (in model mice);
  • Aging of adaptive immunity, cancer, immunotherapy (in model mice);
  • Clonality of CD4+, CD4+Treg, CD8+, and CD8+PD1+ Т lymphocytes in tumors and peripheral blood as a factor for forecasting in color cancer patients (in clinical samples).

The practical value of the study

Scientific results:

  1. The Laboratory has conducted a research of the clonal structure of the repertoires of tumor-infiltrating Т and B lymphocytes in human skin melanoma. We have demonstrated, for the first time, that pronounced presence of clonal hypermutating populations of B lymphocytes and IgG1-producing plasmatic cells as part of tertiary lymphoid structures or in metastasized lymph nodes is associated with a significantly more favorable prognosis. The same trend can be observed for non-papillary bladder cancer as well as lung adenocarcinoma. We are actively working tin this direction.
  2. We have developed, for the first time, an approach to analyzing the repertoires of tumor- infiltrating Т lymphocytes from free DNA blood plasma .
  3. A new approach has been developed to analyzing sorted subpopulations of tumor-infiltrating lymphocytes that combines obtaining informative repertoires of immune receptors and the transcriptome profile.
  4. Using a mouse melanoma model, we have demonstrated the clustered location of clonal populations of T lymphocytes in a tumor. We demonstrated the dependence of the response to therapy using antibodies to PD1 on the emergence of clonal expansions of CD4 and CD8 Т lymphocytes, and the duration of preservation of increased clonality of the repertoire over time. We demonstrated the predominant activation of CD4 Т lymphocytes in response to therapy with blocking antibodies to CTLA-4, the activation of CD4 and CD8 Т lymphocytes in response to therapy with blocking antibodies to PD1, the activation of CD8, CD4, Treg and B lymphocyte in therapy with agonistic antibodies to OX40. 

Education and career development:

  • 5 Candidate of Sciences dissertations have been prepared and defended.
  • On the grounds of the Laboratory two Candidate of Sciences dissertations are now being prepared.
  • We have compiled and implemented the special course «Immunology» for postgraduate students of Privolzhsky Research Medical University in the directions of training 30.06.01 Fundamental medicine, 06.06.01 Biological sciences.
  • Employees of the Laboratory conduct lectures for students at the School of young researchers of the Research Institute of Experimental Oncology and Biomedical Technologies of  Privolzhsky Research Medical University.

Infrastructure transformations:

  • We have furnished the Laboratory with unique world-class equipment to conduct research in immunology.
  • The material and technical base of the university has been enhanced and the level of personnel training has been improved.


  • Institute of Bioorganic Chemistry of the Russian Academy of Sciences (Russia): joint research, joint publications, academic seminars to exchange experience, mutual consulting.
  • Memorial Sloan Kettering Cancer Center (USA), Masaryk University (Czech Republic): joint academic events, joint publications, experience exchange, collaborative analysis of the obtained results.
  • Pirogov Russian National Research Medical University (Russia), Netherlands Cancer Institute (the Netherlands), Institute of Immunology of the Federal Medical-Biological Agency (Russia): joint research, joint publications, academic seminars for experience exchange, mutual consulting.

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izosimova a.v., yuzhakova d.v., skatova v.d., volchkova l.n., zagainova e.v., chudakov d.m., sharonov g.v.
Deciphering Repertoire of B16 Melanoma Reactive TCRs by Immunization, In Vitro Restimulation and Sequencing of IFNγ-Secreting T Cells. International Journal of Molecular Sciences. 2021 Sep (22, 18).
sharonov g.v., serebrovskaya e.o., yuzhakova d.v., britanova o.v., chudakov d.m.
В Cells, plasma cells and antibody repertoires in the tumour microenvironment. Nature Reviews Immunology. 2020 May (20, 5).
zhigalova e.a., izosimova a.i., yuzhakova d.v., volchkova l.n., shagina i.a., turchaninova m.a., serebrovskaya e.o., zagaynova e.v., chudakov d.m., sharonov g.v.
RNA-Seq-Based TCR profiling reveals persistently increased intratumoral clonality in responders to Anti-PD-1 therapy. Frontiers in Oncology. 2020 Apr (10).
isaeva o.i., sharonov g.v., serebrovskaya e.o., turchaninova m.a., zaretsky a.r., shugay m., chudakov d.m.
Intratumoral immunoglobulin isotypes predict survival in lung adenocarcinoma subtypes. The Journal for ImmunoTherapy of Cancer. 2019 Oct (7, 1).
pogorelyy m.v., minervina a.a., shugay m., chudakov d.m., lebedev y.b., mora t., walczak a.m.
Detecting T cell receptors involved in immune responses from single repertoire snapshots. PLOS Biology. 2019 Jun (17, 6).
fan x., moltedo b., mendoza a., davydov a.n., faire m.b., mazutis l., sharma r., pe'er d., chudakov d.m., rudensky a.y.
CD49b defines functionally mature Treg cells that survey skin and vascular tissues. Journal of experimental medicine. 2018 Nov (215, 11).
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