Enhancing anti-tumor immunity through co-blocking PD-L1 and TIGIT by facilitating tumor-directed responses and additional VEGF inhibition
- Author(s)
- Zhu, X; Cui, X; Yu, H; Xu, J; Chen, X; Ren, X; Wei, X; Chen, S; Wang, Y; Fei, L; Xie, B; Li, M; Li, X; Jia, H; Feng, Y; Xia, S; Chen, L; Cheng, Y; Zhang, L; Li, H; Zhu, X; Zhan, Y;
- Journal Title
- Frontiers in Immunology
- Publication Type
- Research article
- Abstract
- Combination therapy targeting the PD-1/PD-L1 and TIGIT pathways has been explored to enhance the efficacy of current immunotherapies. In this study, we investigated strategies to further potentiate the co-blockade of PD-L1 and TIGIT for cancer immunotherapy. Firstly, we demonstrated that the bispecific antibody (HB0036) for PD-L1 and TIGIT co-blockade induced a greater T-cell proliferative response in vitro compared to the combined administration of the parental antibodies. This response was associated with CD226 upregulation and PD-1 downregulation. HB0036 significantly enriched the TIGIT antibody at PD-L1(+) tumors and achieved improved tumor control with favorable immunological characteristics in both syngeneic and xenograft tumor models. Secondly, we showed that tumor control by co-targeting PD-L1 and TIGIT can be further enhanced by additionally blocking VEGF, a key player in tumorigenesis and tumor angiogenesis, in preclinical studies. Lastly, considering the heterogeneity of tumors, we analyzed how the expression patterns of PD-L1 and CD155 influence T cell responses. We also examined the spatial distribution of PD-L1 and CD155, along with related immunological parameters from patient samples, to assess the potential of PD-L1 and TIGIT co-blockade in diverse tumor contexts.
- Publisher
- Frontiers
- Keywords
- Animals; *Receptors, Immunologic/antagonists & inhibitors/immunology/metabolism; *B7-H1 Antigen/antagonists & inhibitors/immunology/metabolism; Mice; Humans; *Vascular Endothelial Growth Factor A/antagonists & inhibitors/immunology; *Neoplasms/immunology/therapy; Cell Line, Tumor; *Antibodies, Bispecific/pharmacology; Immunotherapy/methods; T Lineage-Specific Activation Antigen 1; Xenograft Model Antitumor Assays; Female; Immune Checkpoint Inhibitors/pharmacology; Antigens, Differentiation, T-Lymphocyte; T-Lymphocytes/immunology; Receptors, Virus; Pd-(l)1; Tigit; TME (tumor microenvironment); Treg - regulatory T cell; Vegf; bispecific antibody; combination (combined) therapy
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.3389/fimmu.2025.1746155
- Open Access at Publisher's Site
https://doi.org/10.3389/fimmu.2025.1746155- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-02-03 06:11:44
Last Modified: 2026-02-03 06:11:50