Abstract 1985P
Background
Tumor cells express many immunosuppressive molecules that change their functional state and begin to support tumor growth. The aim of this work is to determine the number of PD-1 and TIM-3 molecules to assess the level of depletion of functional properties and impaired cytotoxic functions in breast cancer patients.
Methods
We determined the cytotoxic activity of PBMCs from breast cancer (BC) patients and healthy women against the tumor cell line ZR-75-1 by the non-radioactive cytotoxic test CytoTox96. The absolute number of surface receptors on the cells and absolute cell counts were detected by QuantiBRITE PE (BD Biosciense) and Precision Count Beads (Biolegend), respectively.
Results
We found that BC patients had significantly more PD-1+ CD4 and CD8 cells as well as TIM-3+ CD8 cells than healthy donors. The number of molecules per cell for PD-1+ cells was significantly lower in BC patients than in healthy donors and for TIM-3 this pattern is observed only for TIM-3+ CD8 cells. Thus, we showed that the cytotoxic activity of donors’ PBMCs was significantly higher compared with that of breast cancer patients. The cytotoxic activity of PBMCs in BC patients correlated with an increase in PD-1+ and TIM-3+ CD4 and CD8 cell density, an increase in the absolute number of TIM-3+ CD4, TIM-3+ CD8 and PD-1+ CD8 cells as well as with a decrease in the number of molecules per cell for TIM-3+ CD8 cells and PD-1+ CD4 cells, respectively.
Conclusions
PBMCs of BC patients are characterized by an increased number of PD-1+ and TIM-3+ cells with fewer number of the molecules on them. The cytotoxic activity of BC patients’ PBMCs is reduced, which correlates with the number of PD-1 and TIM-3+ cells and the distribution of these molecules on the cell surface. The work was supported by the Grant of the President (No. 075-15-2019-281).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Federal State Budgetary Institution \"Research Institute of Fundamental and Clinical Immunology.
Funding
Grant of the President (No. 075-15-2019-281).
Disclosure
All authors have declared no conflicts of interest.