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

Abstract

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.

The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer—Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy

“…It inhibits effector T cell activation in vivo and NK cytotoxicity by binding to CD115 and CD112 molecules on dendritic cells (DCs) and macrophages (TAMs/MФ), but also to ligands on the tumour cell surface, thus facilitating the mechanisms of immune escape in the cancer immune cycle [ 405 , 406 , 407 , 408 ]. Importantly, TIGIT and programmed death-ligand 1 (PD-1) have been shown to be upregulated on tumour antigen-specific CD8 + T cells and CD8 + tumour infiltrating lymphocytes (TILs) in both HNSCC patients and mouse models; in addition, their level was correlated with other immune-checkpoint molecules, i.e., PD-1, TIM-3 and LAG-3 [ 409 , 410 , 411 ]. Therefore, a few clinical trials on TIGIT-blockade have recently been initiated, predominantly in combination with immune checkpoint co-blockade therapy against PD-L1 used in different human solid cancers [ 410 , 412 , 413 , 414 ].…”

Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends

“… 53 The dual blockade of the TIGIT and PD-1 axis stimulates the effective T cells and NK cells in ovarian cancer patients. 54 The most promising anti-TIGIT mAbs include tiragolumab (GO30103), zimberelimab (AB122), and tislelizumab (BGB-A317). In the CITYSCAPE trial, median PFS increased from 3.6 months (atezolizumab) to 5.4 months (tiragolumab plus atezolizumab) in 135 NSCLC patients.…”

Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors

“…Ovarian cancer at FIGO stages I and II is accounted as curable, and the five-year survival rates total 90% and 70%, respectively. In comparison, at the advanced stages of OC, the five-year survival rate drops below 30% [ 2 , 3 , 4 , 5 ].…”