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Abstract
Currently, immune checkpoints inhibitors (ICIs) are widely used in clinical practice. However, for a significant group of patients, monotherapy with an ICI is not effective. One of the reasons for this lies in the complex mechanism of interaction between receptors and ligands of different ICs, which are simultaneously present on the cell surface. Simultaneous inhibition of various ICs is considered as one of possible solutions to this problem. Clinical trials of ICI combinations are currently underway. Some of these combinations are approved for use in clinical practice. The signaling pathways associated with ICs are being actively studied. Targeting of these pathways together with ICIs is a new therapy strategy. This review summarizes data on PD-1/PD-L1 and TIM-3/Gal-9 immune checkpoints as a promising targets of ICI combination. The signaling pathways associated with the molecules of these ICs have also been characterized. The prospect of therapies based on simultaneous blocking of PD-1, PD-L1, TIM-3, Gal-9 molecules and their signalling pathways were evaluated.
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