Tumor microenvironment (TME) plays a critical role in regulating immune responses to tumors. UTHealth Houston and UTSW researchers discovered certain membrane tyrosine kinase Eph receptors, including EphA7 and EphB1, specifically bind to the immune inhibitory receptors leukocyte Ig-like receptor family B 5 (LILRB5) and result in bi-directional signaling. They further developed novel anti-LILRB5 monoclonal antibodies (mAbs) and demonstrated their therapeutic potentials in vitro and in vivo.
Background
Current immune checkpoint blockade therapies have been successful in treating certain types of solid cancer. However, most cancer patients do not respond to such treatment, or they relapse after treatment. In addition, immune checkpoint blockade monotherapies has not yet successfully treated hematologic malignancies, such as multiple myeloma and leukemia. Immunosuppressive myeloid cells are critical obstacles to T cell–centered immune checkpoint blockade therapies. However, it is still unclear how tumor cells interact with myeloid cells to regulate immune responses and tumor development.
Significance and Impact
Researchers at UTHealth Houston and The University of Texas Southwestern Medical Center (UTSW) discovered that certain Eph receptors functionally interact with the myeloid checkpoint receptor LILRB5 resulting in bi-directional signaling, and LILRB5 plays an important role in supporting immunosuppressive myeloid cells and sustaining tumor development. They further developed novel anti-LILRB5 monoclonal antibodies (mAbs) and demonstrated that Eph-induced LILRB5 signaling and functions were reversed by LILRB5 blockade, which significantly reduced immunosuppressive marker expression in vitro and suppressed tumor development in vivo. These results indicate anti-LILRB5 mAbs may be an attractive immunotherapy to certain patients with cancer.
Benefits/Technology Advantages
•LILRB5 blockade via anti-LILRB5 antibodies suppressed tumor growth, decreased the MFI of immunosuppressive marker CD206, and increased effector CD8+ T cell numbers in the TME in vitro.
•Anti-LILRB5 mAbs suppressed tumor development in the mouse tumor model with human LILRB5 gene expression.
Related Publications
He, Yubo, et al. "Eph receptors activate myeloid checkpoint receptor LILRB5 to support tumor development." Cancer Immunology Research 13.6 (2025): 821-835.