Cancer immunotherapy laboratory
Grant Agreement No.: 14.W03.31.0005
Project name: Clonal composition of tumor-infiltrating T lymphocytes as a prognostic and predictive marker in cancer treatment
Name of the institution of higher learning: State Educational Establishment of Higher Professional Training Nizhny Novgorod State Medical Academy of the Ministry of Public Health of the Russian Federation
Fields of scientific research: Fundamental medicine
The project aims at studying the role of the clonal composition of different functional subpopulations of T lymphocytes in tumor immunosurveillance and throughout the development of antitumor response.
We are interested in:
-studying how immunosuppressive tumor activity affects the clonal and functional structure of the tumor-infiltrating T lymphocytes;
-studying how immunotherapy using checkpoints inhibitors can affect the established relationship between the tumor and adaptive immunity, clonal composition of tumor-infiltrating, and in particular tumor-specific T lymphocytes;
-establishing clonal diversity of the tumor-infiltrating T lymphocytes subsets and specific subsets of blood T lymphocytes (such as CD8+PD1+) as a prognostic marker in drug therapy, and developing approaches to rational interpretation of this information for designing patient-specific immunotherapeutic intervention;
-analyzing age-related differences in abundance and repertoire of tumor-specific T lymphocytes, and the response to various types of immunotherapy to better define the role of adaptive immunity aging on cancer progression and treatment. Studying the ways to support antitumor T cell immunity in the elderly.
-performing a detailed study of the interplay between adaptive immunity and structural organization of the tumor by analyzing the changes in tumor structure in response to immunotherapy with checkpoint inhibitors and correlation of various tumor parameters and the state of T cell repertoire.
To answer these and related questions, we will use several animal models and clinical samples. Within the Laboratory, we need to combine the competence of professionals working with tumor models and populations of blood cells, the experience of clinicians, microscopists, molecular biologists, and bioinformatics. It is important that all the necessary components are well represented present in
the team. This interdisciplinary character of the Lab will allow us to spend quite a comprehensive study of the problem of clonal diversity of functional subpopulations of tumor-infiltrating and tumor-specific T lymphocytes. Key objective of the project and created Laboratory is a detailed study of the clonal repertoire of functional subpopulations of tumor-infiltrating T lymphocytes and establishing its role as a prognostic and predictive marker in terms of tumor development and the potential efficacy of immunotherapy.
From the fundamental point of view, we expect that the use of modern analysis technologies such as T cell receptor repertoire analysis will allow us to gain novel insights into complex questions regarding the interplay between tumor and adaptive immunity. Being among the pioneers in the field of immune repertoire profiling and having an extensive experience in this cutting edge technique allows us to expect results worthy of publication in high-ranking journals.
Direct interdisciplinary interaction with clinicians during the course of the project should accelerate the development and establishment of modern methods of diagnostic analysis, tumor monitoring and personalized immunotherapy in Russia. Moreover, we expect that the results obtained by Laboratory will lead to a deeper understanding of the algorithms of interaction between tumor and adaptive immunity, and will thus lay the foundation for further development of novel, more efficient and effective approaches to cancer immunotherapy.
Chudakov Dmitriy Mikhailovich
Date of Birth: 13.09.1978
Academic degree and title: D.Sc.
Job Title: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry,
Field of scientific interests: molecular biology, bioinformatics, high-throughput sequencing, molecular barcoding, adaptive immunity, T-cell receptor repertoire, antibody repertoire, aging, autoimmunity, HSCT, cancer, immunotherapy
One of the most cited young scientists of Russia. Presidential Award in Science and Innovation for Young Scientists, 2012. Co-author of more than 90 publications in peer-reviewed journals, including 20 publications in the main Nature group journals. Specialist in molecular biology, microscopy, bioinformatics. Developer of the widely used palette of fluorescent proteins. Since 2009, develops and applies molecular and bioinformatics methods for T cell receptor (TCR) and antibody repertoire analysis using high-throughput sequencing. First introduced unique molecular barcoding for TCR profiling, which dramatically increased the accuracy of the analysis. Performed a series of biomedical research: adaptive immunity aging, consequences of immunosuppressive therapy and blood cells transplantation, generation of functional TCR repertoire, TCR repertoires of mother and child, twins, and unrelated donors, TCR repertoires in autoimmunity, identification of tumor-specific TCRs. Approaches and methods developed by Chudakov DM are used worldwide.