Fig. 3

Drug resistance mechanisms of chemotherapy and immunotherapy. Nasopharyngeal carcinoma cells could develop various drug resistance mechanism against anticancer therapy. A Chemotherapeutic agents exert the anticancer effect through DNA damage and induce cell apoptosis. Upregulation of proteins and miRNAs can inhibit apoptosis and directly confer cell drug resistance phenotype. B Tumor cells can develop drug resistance towards immunotherapy through the interaction with tumor microenvironment. Immune effector cells are able to identify and kill tumor cells through immune infiltration into the tumor site. Granzyme B and D can inhibit the immune infiltration process. Annexin A2 can stimulate Dendritic cells to produce IL-10, which has inhibitory effect on cytotoxic CD8⁺ T cells. Pro-inflammatory cytokines IL-6 and IFN-γ can decrease CD4/CD8 T cell ratio. Cancer-associated fibroblasts (CAF), tumor-associated macrophages (TAM), and myeloid derived suppressor cells (MDSC) can inhibit the activity of immune effector cells. Tumor cells can activate alternative pathways to circumvent PD-1/PD-L1 blockade