The Dual Blockade of the TIGIT and PD-1/PD-L1 Pathway as a New Hope for Ovarian Cancer Patients

Simple Summary Ovarian cancer (OC) is the most lethal gynecological malignancy with a five-year survival rate of 47%, followed by cervical cancer (66%), and uterine cancer (81%). Despite the success of immunotherapies based on the programmed cell death pathway (PD-1/PD-L1) in other solid cancers, the response of OC patients is low. The promising approach in OC treatment seems to be a combined therapy, including other immune checkpoints such as the TIGIT/CD155/DNAM-1 axis. The approach may trigger the synergistic effect, break the immunosuppression in the ovarian cancer tumor microenvironment, and enhance the expression of tumor antigens. The dual blockade stimulates the effector activity of T cells and NK cells, and redirects the immune system activity against tumor cells. The current understanding of the activity of both pathways, TIGIT/CD155/DNAM-1 and PD-1/PD-L1, as well as their synergistic action in OC, remains unclear. The prognosis for ovarian cancer (OC) patients is poor and the five-year survival rate is only 47%. Immune checkpoints (ICPs) appear to be the potential targets in up-and-coming OC treatment. However, the response of OC patients to immunotherapy based on programmed cell death pathway (PD-1/PD-L1) inhibitors totals only 6-15%. The promising approach is a combined therapy, including other ICPs such as the T-cell immunoglobulin and ITIM domain/CD155/DNAX accessory molecule-1 (TIGIT/CD155/DNAM-1) axis. Preclinical studies in a murine model of colorectal cancer showed that the dual blockade of PD-1/PD-L1 and TIGIT led to remission in the whole studied group vs. the regression of the tumors with the blockade of a single pathway. The approach stimulates the effector activity of T cells and NK cells, and redirects the immune system activity against the tumor. The understanding of the synergistic action of the TIGIT and PD-1/PD-L1 blockade is, however, poor. Thus, the aim of this review is to summarize the current knowledge about the mode of action of the dual TIGIT and PD-1/PD-L1 blockade and its potential benefits for OC patients. Considering the positive impact of this combined therapy in malignancies, including lung and colorectal cancer, it appears to be a promising approach in OC treatment.