Dr. Xiaoyang Qi, Professor

Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, USA

Biography

Dr. Xiaoyang Qi is a professor in the Division of Hematology-Oncology in the Department of Internal Medicine at the University of Cincinnati College of Medicine. The laboratory of Dr. Qi focuses on cell membrane phospholipids and proteins as specific therapeutic targets and diagnostic biomarkers for cancer and genetic diseases. His research is focused on developing a new saposin C (SapC) coupled dioleoylphosphatidylserine (DOPS) nanovesicle which has the potential to offer a targeted, potent, broad, and safe therapeutic agent for cancer patients.

Topic

Cancer Immunotherapy: Impeding Hsp70–TLR2 Axis for MerTK downregulation

Abstract

Despite significant advancements in cancer treatment, a major challenge remains in overcoming the immunosuppressive tumor microenvironment (TME) that hinders effective anti-tumor immunity. Immunosuppressive M2 macrophages (MΦs) in the TME facilitate escape from immune surveillance and promote tumor growth. One key player in this suppression is MerTK (Myeloid-epithelial-reproductive tyrosine kinase), which promotes tumor immune evasion through various mechanisms. This study investigates a novel therapeutic approach centered on interrupting the interaction between cancer-secreted heat shock protein 70 (Hsp70) and Toll-like receptor 2 (TLR2) to downregulate MerTK expression and reverse immune tolerance. Hsp70, often found on the surface of tumor cells, engages with TLR2 on immune cells, initiating signaling cascades that ultimately lead to increased MerTK expression and the promotion of a pro-tumoral phenotype. By employing specific lipid vesicles (LVs) to impede the Hsp70–TLR2 axis, we hypothesized that the downstream signaling can be interrupted, thereby reducing MerTK levels. Our findings demonstrate that sequestering of cancer-secreted Hsp70 by tumor-targeting saposin C (SapC)-based LVs to block the M2 MΦ polarization through disrupting the Hsp70-TLR2-MerTK interaction. These results suggest that targeting the Hsp70–TLR2 axis represents a novel and effective strategy for downregulating MerTK, offering a potent adjunct to existing immunotherapies and providing a potential pathway to overcome resistance in a broad range of cancers.