In order to improve the anti-tumor efficacy of PD-1/PD-L1 inhibitors, combination therapies with other immune checkpoint targeting antibodies, chemotherapy, radiotherapy, and tumor neoantigen vaccine that target resistance mechanisms and enhance the different components of the immune system were utilized and succeeded in treating advanced and poorly immunogenic tumors in pre-clinical and clinical models (23, 24). The gene discussed is PDCD1; the disease is neoplasm.