PVR (PVR Cell Adhesion Molecule)

Overall, our findings provide strong evidence for the efficacy and safety of CD155-based CAR T-cell therapy in cervical and breast cancer. This study contributes to the growing body of research supporting the potential clinical application of CD155-targeted immunotherapy for patients with cervical and breast cancer.

Our findings suggest that TIGIT and CD96 could be markers of the clinical stage and treatment response of HNSCC. Therefore, administering anti-TIGIT and anti-CD96 after radiotherapy may provide a novel approach for incorporating immunoradiotherapy into HNSCC treatment.

Collectively, our data provide novel molecular insights into the immunoregulatory role of CD155 and establish epitope-specific mAbs as valuable tools for studying immune checkpoint pathways. This study provides a framework for developing CD155-targeted immunotherapies and enhances the understanding of immune escape mechanisms in cancers.

HCC tissues with high PVR expression were more common in metastatic disease and were associated with an immune-cold TME. These findings may have implications for the development of immunotherapies for HCC.

This study unveils a novel mechanism by which arecoline promotes immune evasion in OSCC and highlights promising immune therapeutic targets and strategies for the treatment of areca nut-associated OSCC.

Further, patient-derived PDAC organoids were treated with the standard of care therapies FOLFIRINOX, gemcitabine plus paclitaxel, or the antibody-drug conjugate enfortumab vedotin...Targeting Nectin-4 with the antibody-drug conjugate enfortumab vedotin inhibited tumor growth in multiple patient-derived PDAC organoids. Collectively, our data underscores Nectin-4 as a novel therapeutic target and provides the rationale to test this agent in PDAC patients.

Previous studies have shown that inhibition of the E1 enzyme, which catalyzes the small ubiquitin-like modifiers (SUMO), with the small molecule TAK-981, can reprogram the TME to enhance immune activation and suppress tumor growth...Mechanistic studies suggest that SUMO E1 inhibition enhances antibody-mediated elimination of Tregs through innate immune cells, potentially by activation of type I interferon responses. Our results highlight a mechanism to enhance the efficacy of anti-TIGIT therapy.

Quantitative spatial profiling of the PD-1/PD-L1 and TIGIT/CD155 suppression pathways using novel AQUA algorithms could help predict patient outcomes and ACT responses reliably, guiding development of more effective personalized management for PASC.

HSP47 inhibition promotes immune evasion by upregulating CD155 via the TRAF2-NF-κB pathway, which impairs CD8+ T cell-mediated antitumor immunity. The combination of HSP47 inhibition with CD155/TIGIT blockade enhances therapeutic efficacy, suggesting a promising strategy for combination cancer therapies.

In addition, the shed ectodomain of TIGIT maintains binding to CD155 and the tested clinical anti-TIGIT antibody, tiragolumab. Given the significant anti-TIGIT failures, these unexpected findings reveal potential saturation vulnerabilities of macaque CD155 and preclinical TIGIT antibodies by soluble shedded TIGIT ectodomain, contrary to the intended mechanism of action on the lymphocyte membrane. These results caution against extrapolation and question the suitability of cynomolgus and rhesus macaques for preclinical safety and dose estimation of TIGIT-targeted therapies.

This study identifies a previously unrecognized master regulator CCNC that functions as a suppressor of CD155-mediated cancer immune evasion. The findings of this study suggest that tumors with low CCNC expression may be resistant to monotherapy and highlight a combination immunotherapy (TIGIT/PD-1 co-blockade) as a promising anti-cancer therapeutic strategy to overcome immune evasion in CCNC-deficient tumors.

The PVR-TIGIT/CD96/CD226 axis is a critical immune checkpoint in glioma. Targeted disruption of this pathway offers a promising strategy to overcome resistance and improve clinical outcomes.