Immunology Research Program

ABSTRACT: IMMUNOLOGY PROGRAM The Immunology Program (IMM) is devoted to enhancing our understanding of the function of the innate and adaptive immune system in the pathogenesis of malignant disease. There are four specific aims: (1) Elucidate new roles for innate immune receptors and the microbiome in carcinogenesis; (2) Uncover novel functions of diverse immune cells and pathways in the tumor microenvironment; (3) Develop novel approaches to use immunotherapy to treat patients with cancer; (4) Discover new targets for improving the outcome of patients with malignant disease undergoing allogeneic stem cell transplantation (allo-SCT). There are 24 program members from six different departments at UNC School of Medicine. Members have $13.2M (direct costs) cancer-related funding including; $2.8M in direct costs from NCI and $6.8M in in direct other peer and other NIH. NCI funding has increased 145% since the last submission. Highlights of the program include discoveries of new roles of innate immune receptors in colorectal cancer; importance of microbiota on cancer-relevant immune cell populations; a comprehensive immunogenomic characterization of the tumor microenvironment for TCGA and critical roles for T follicular helper and B cells during checkpoint inhibitor therapy in breast cancer. Significant translational findings include the new use of antigens expressed on solid tumors as targets for chimeric antigen receptor modified T cell therapy (CAR T) including B7-H3 for pancreatic cancer and glioblastoma, and CD138 for multiple myeloma. IMM is led by Jenny Ting PhD, William Rand Kenan Professor of Genetics, Microbiology-Immunology (M-I) and Director of the Translational Immunology Center who is a world’s expert on innate immune receptors, and Jonathan Serody MD, Elizabeth Thomas Professor of Medicine, M-I and the Associate Director for Translational Sciences in the Cancer Center, who is an expert on the biology of GVHD, tumor vaccines and the tumor microenvironment. IMM leadership works closely with CR to translate findings from IMM. These include the evaluation of CD30-specific CART T cells in the treatment of CD30-expressing lymphomas, B7-H3-specific CAR T cells in relapsed ovarian cancer and GD2-specific CAR T cells in neuroblastoma. Six outstanding faculty members have been recruited since the last grant submission. IMM has a strong publication record with 359 papers; 18% intra-programmatic, 39% inter-programmatic publications and 33% of the papers were in journals with an impact factor > 10. IMM has a strong record of training with two training grants focused on tumor immunology or immunotherapy. Research within IMM has been significantly informed by the Office of Outreach and Community Engagement with an emphasis on cancers in the catchment area, including breast, colorectal, pancreatic cancers and multiple myeloma.