Figure 2.
Combination strategies aimed at relieving the immunosuppressive tumor microenvironment with chemotherapy and potentiating cytotoxic T cells with immune checkpoint inhibitors. The tumor microenvironment is characterized by the presence of various immune cell types, including different subsets of adaptive immune cells and TAMs, MDSCs, and Tregs. The latter dampens the anti-cancer activity of T cells through several mechanisms. Moreover, cancer cells and myeloid cells express PD-L1/PD-L2 and APCs express CD80/CD86. Binding of these molecules to PD-1 and CTLA-4 respectively, expressed on T cells, results in inhibitory signals that counteract T cell activation and function. The immunomodulatory properties of different types of chemotherapeutic drugs can be exploited to enhance anti-tumor immunity. By optimally matching the immunomodulatory features of specific chemotherapeutic drugs with the T cell-boosting effect of immune checkpoint inhibitors, the efficacy of immunotherapy might be improved.