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Welcome to the Zhu Lab
Yuwen Zhu, PhD
Research Interests
My research focuses on developing novel agents for cancer immunotherapy. I am interested in understanding how the tumor microenvironment actively limits effector immune cell infiltration and functions.
Active Research Projects
Novel Immune Checkpoints
My lab is the first to identify CD112R (also called PVRIG) as a new T cell immune checkpoint within the TIGIT/CD226 network. We recently found the BigLEN/GPR171 axis as a novel immune checkpoint pathway to regulate antitumor T cell immunity. Using knockout mice and blocking monoclonal antibodies, we are better characterizing the roles of these two interesting pathways in immune-related diseases. At the same time, we are actively developing therapeutic agents for clinical application.
Pathways That Limit Intratumoral Effector T Cell Infiltration
Immunologically cold tumors are refractory to ICB therapy because of their lack of effector immune cells within tumors. In addition to cancer immunogenicity, the TME is detrimental to the infiltration and functions of effector immune cells. My lab is interested in characterizing these pathways or mechanisms, and by targeting these, we aim to develop therapeutic agents to improve effector T cell infiltration and then to sensitize immunologically cold tumors to ICB therapy. The CD93/IGFBP7 axis is a key pathway we identified that contributes to tumor vascular dysfunction and thereby T cell exclusion. Our finding directly led to a first-in-class clinical trial with CD93 mAb in solid cancers (NCT05785754). The most recent work in the lab has led to the finding of GPR182, a lymphatic chemokine scavenger, which acts as a brake to limit effector T cell infiltration in melanoma. Currently we are working on a therapeutic monoclonal antibody against GPR182 for cancer immunotherapy.