Molecular mechanisms of breast cancer chemoresistance by immune checkpoints

Progression of resistance to chemotherapy in breast cancer (BC) has been recognized as a main factor in decreasing the survival of patients with this malignancy. Recent investigations have described the involvement of immune checkpoint molecules in the progress of drug resistance in breast carcinoma patients. In the present study, the molecular participation of immune checkpoint factors in chemoresistance of BC both in-vitro and in-vivo is reviewed. Numerous immune checkpoints such as PD-1/PD-L1, CTLA-4, B7-H3, B7-H4, B7-1, and B7-2 have been specified as positive regulators of resistance to various drug types in BC. In several molecular pathways of drug resistance in BC, immune checkpoints affect the chemoresistance of this cancer in a drug- and cell-type-dependent manner. In addition, immune checkpoints promote chemoresistance in response to particular drugs in specific BC cell lines. Furthermore, several the immune checkpoint molecules have not been evaluated in the field of the chemoresistance in breast malignancy either in-vitro or in-vivo. Overall, investigations have indicated that targeting immune checkpoint molecules may be considered as a novel method to improve existing anti-BC treatments.