AP19678934 “Role of glycogen synthase kinase-3α in generation of myeloid-derived suppressor cells”

Description of the project

Pre-clinical and clinical studies have well documented that aberrant expansion and accumulation of MDSCs in animal tumor models and cancer patients act as a negative regulator of anti-tumor immune response and a hurdle for immunotherapy against cancer. Therefore, elucidation of underlying molecular mechanisms of constitutive MDSC expansion and thereby dampening the immunosuppressive tumor environment to allow the eradication of tumor cells by inherent immunity or by immunotherapeutic approaches is the utmost urgent task in front of basic researchers and clinicians.

The aim of the Project

The project’s goal to examine the possible involvement of GSK-3α in the generation of MDSCs.

Expected results

We expect the kinase activity of GSK-3α is required for the generation and maintenance of the suppressor phenotype of MDSCs. Thus, we will expect the following immediate results: 1) siRNA-mediated silencing of GSK3α will result in attenuating of the immunosuppressive function of the ex vivo generated MDSC. 2) siRNA-mediated silencing of GSK3α will result in changing in activation/phosphorylation pattern of STAT3 and NF-κB transcription factors.

Socio-economic impact of the project results

Due to the fundamental nature of the project, there will not be immediate socio-economic impact. However, expected results and subsequent studies in the near future will provide useful information for the designing of wise therapeutic approaches to target aberrantly accumulated MDSCs in cancer patients thereby increasing immunotherapeutic efficiency. It will eventually alleviate the major economic burden associated with fighting against cancer in every single country in the world including Kazakhstan.

Area of application

Cellular and molecular immunology.

Information for the potential users

MDSCs are heterogeneous immature myeloid cells that expand as a result of emergency myelopoiesis during various inflammatory conditions such as infection and cancer. Pre-clinical and clinical studies have well documented that aberrant expansion and accumulation of MDSCs in animal tumor models and cancer patients act as a negative regulator of anti-tumor immune response and a hurdle for immunotherapy against cancer. Therefore, elucidation of underlying molecular mechanisms of constitutive MDSC expansion and thereby dampening the immunosuppressive tumor environment to allow the eradication of tumor cells by inherent immunity or by immunotherapeutic approaches is the utmost urgent task in front of basic researchers and clinicians.

Research team

1. N. Abdollah, Ph.D (biology), project supervisor, acting head of the laboratory. H-index: 6. ORCID: https://orcid.org/0000-0002-4769-7824. Scopus ID: 57194001982.Web of Science ID: R-2193-2016.

2. A. Kaly, MSc (life science), senior researcher. H-index: 3. ORCID ID: https://orcid.org/0000-0002-5129-1165. Scopus ID: 57195580717. Web of science ID: AAF-9781-2020.

3. R. Tleulieva, Ph.D, leading researcher. H-index: 6. ORCID ID: https://orcid.org/0000-0001-8897-9986. Scopus ID: 6507202148. WoS ID: N-5634-2017.

4. Yu. Perfilyeva, Ph.D (biology), leading researcher. H-index: 7. ORCID: https://orcid.org/0000-0001-6803-0773. Scopus ID: 56823500600. Web of Science ID: AAF-9666-2020.

5. G. Daulet, Ph.D