TIGIT enhances CD4⁺ regulatory T‐cell response and mediates immune suppression in a murine ovarian cancer model

Abstract

Ovarian cancer (OC) is the fifth‐leading cause of cancer‐related death in women with a pathogenesis involving activation of regulatory T cells (Tregs). The T‐cell immunoglobulin and ITIM domain (TIGIT) is a well‐known immune checkpoint molecule that inhibits T‐cell responses. However, the role of TIGIT in OC is not comprehensively understood. In this study, we revealed crucial functions of TIGIT in the development and progression of OC. ID8 cells were used to establish a murine OC model. TIGIT expression was increased in immune cells of OC mice, particularly in CD4+ Tregs. Anti‐TIGIT monoclonal antibodies (mAb) were used to block the function of TIGIT in OC mice, and we found that the anti‐TIGIT treatment reduced the proportion of CD4+ Tregs, but did not affect CD4+ and CD8+ T cells or natural killer cells. Splenic CD4+ Tregs from OC mice were isolated after the anti‐TIGIT treatment, and their functioning was examined. Inhibition of TIGIT lowered the degree of immunosuppression induced by CD4+ Tregs. A survival curve suggested that anti‐TIGIT treatment can improve the survival rate of OC in mice. We conclude that TIGIT enhanced CD4+ Tregs response and mediated immunosuppression in the OC model. Our data suggest that inhibition of TIGIT is a potential therapeutic target in OC patients.

Identification of Prognostic Biomarkers Among FAM83 Family Genes in Human Ovarian Cancer Through Bioinformatic Analysis and Experimental Verification

“…41 Chen et al demonstrated that TIGIT, a well-known immune checkpoint, could enhance CD4+ regulatory T cell responses and mediate immunosuppression in a murine OC model. 42 Meanwhile, the presence of CD8+ TILs was correlated with a favorable prognosis in patients with epithelial OC. 43 Interestingly, our results showed that CD4+ T cells were positively correlated with FAM83D, and CD8+ T cells were negatively correlated with FAM83D.…”

TIGIT as a therapeutic target of HPV-positive head and neck squamous cell carcinomas

“…Perhaps the mEER HPV-positive HNSCC model has a higher frequency or abundance of TIGIT on Tregs than the Tgfbr1/Pten double knockout model of HPV-negative HNSCC. Intratumoral Treg depletion has been reported with several anti-TIGIT antibodies (e.g., the CT26 colon model) (41,53,54), due to higher Fc affinity for FcyR and stronger induction of ADCC.…”

Poliovirus receptor (PVR)-like protein cosignaling network: new opportunities for cancer immunotherapy

“…In addition, TIGIT regulates Treg function. As mentioned above, Tregs are superior in suppressing T cell activation, and anti-TIGIT treatment reduces the proportion of CD4+ Tregs and inhibits the suppressive ability of Tregs [39][40][41][42], suggesting another pathway for cancer immunotherapy.…”