Rational combination of immunotherapy for triple negative breast cancer treatment.

Recent evidence indicates that tumor infiltrating lymphocytes (TILs), including cytotoxic T cells, are present in the tumor microenvironment of triple-negative breast cancers (TNBC). Despite the presence of cytotoxic T cells, these tumors still develop, progress, and metastasize, suggesting evasion of immune response. One mechanism of immunosuppression is the presence of the T cell inhibitory molecule, programmed death protein 1 (PD-1), on infiltrating T cells and its cognate ligand programmed death ligand 1 (PD-L1) on tumor cells, myeloid dendritic cells (DCs), and macrophages, in the tumor microenvironment. Because TNBC is immunologically insensitive, combinatorial strategies may be ideal to increase both anti-proliferation activity and cytotoxic T cells activity in TNBC. On the basis of two recently discovered regulatory mechanisms of PD-L1, we discuss the potential interactions to boost anti-tumor immunity against TNBC in this review and propose therapeutic strategies that could reduce PD-L1 expression by chemotherapeutic drugs or targeted therapies and sensitize TNBC to immunotherapies.