CITO Seminar: Yang-Xin Fu, MD, PhD
Targeting Tumor Cells to Trigger Immunity
Yang-Xin Fu, MD, PhD
Mary Nell and Ralph B. Rogers Endowed Professorship in Immunology
Professor of Pathology
UT Southwestern Medical Center
Tumor cells express oncogenic receptors that promote growth and evasion of the immune system. Tumor targeting antibodies are designed to kill tumor cells through stress-induced apoptosis, antibody-dependent cytotoxicity, complement-dependent cytotoxicity, and increased phagocytosis. This research revealed that anti-Her2/neu-mediated tumor regression depends on MyD88, interferon, and CD4+ or CD8+ T cells, and that anti-CD20-mediated tumor eradication largely depends on interferon and CD8 expression. CD47 is highly expressed on stem-like cancer cells that are more resistant to conventional treatment. Tumor cell regression by the local anti-CD47 antibody was found to depend on the cGAS/STING pathway and not on CD8+ T cells, MyD88 or interferon molecules. Overall, these studies uncover distinct mechanisms for targeted therapy to elicit tumor regression and may open new avenues for combinational therapies with conventional drugs and immunotherapies.