PD-1/PD-L1 Immunotherapy: Combating Drug Resistance in Breast Cancer

In recent years, immune-checkpoint blocking therapy targeting the PD-1/PD-L1 axis has advanced tumor immunotherapy to a new level, with positive outcomes in a variety of malignant tumors. Tumors can avoid an antigen-specific T cell immune response by means of PD-1/PD-L1 signaling, which adversely controls T cell-mediated immune response. In clinical practice, it was shown that while some patients did have long-term success with immunotherapy, the majority eventually had resistance to drugs and recurrence. Hence, one of the main challenges that severely restricts the long-lasting benefits and widespread use of PD-1/PD-L1 blocking treatment is both primary and acquired resistance. Therefore, it is high time to understand the mechanisms of resistance for improving anti-PD-1/PD-L1 efficacy. In this review, we describe major signaling pathways that regulate PD-1/PD-L1 axis in cancers as well as the role of PD-1/PD-L1 in breast cancer development and progression. In addition, we further discuss the involvement of PD-1/PD-L1 axis in multi-drug resistance in cancers, which affected breast cancer and other solid tumor response rates and durability to treatment strategies.