Description of Research Expertise
My laboratory incorporates both basic science research and clinical investigation to examine the role of innate immunity, in particular monocytes/macrophages, in regulating tumor biology in pancreas cancer as well as other upper gastrointestinal malignancies. Our central hypothesis is that macrophages are key regulators of tumor biology.
Clinical research in the laboratory uses patient-derived samples to understand the role of macrophage biology in metastatic disease and therapeutic efficacy.
Preclinical research in the laboratory uses a genetically engineered mouse model of pancreas cancer in combination with advanced imaging strategies to study macrophage biology within the tumor microenvironment. This preclinical research platform allows for the study of basic immune biology within the tumor microenvironment as well as the rapid screening of novel immunotherapeutic strategies, including cell and gene therapies, for the treatment of cancer.
Studies in the laboratory focus on understanding 1) the signaling pathways that regulate cross-talk between macrophages and tumor cells in vivo, 2) the role of hematopoietic and non-hematopoietic cells in regulating macrophage biology within tumors, 3) the cellular trafficking of macrophages to primary and metastatic lesions, 4) strategies to harness macrophages for anti-tumor therapy, and 5) the impact of chemotherapy/radiation therapy on macrophage biology within tumors.
Andrew H Ko, Alexander C Jordan, Evan Tooker, Simon F Lacey, Renee B Chang, Yan Li, Alan P Venook, Margaret Tempero, Lloyd Damon, Lawrence Fong, Mark H O'Hara, Bruce L Levine, J Joseph Melenhorst, Gabriela Plesa, Carl H June, Gregory L Beatty: Dual Targeting of Mesothelin and CD19 with Chimeric Antigen Receptor-Modified T Cells in Patients with Metastatic Pancreatic Cancer Molecular Therapy
28 (11): 2367,2020.
Lee J.W., Stone M.L., Porrett P.M., Thomas S.K., Komar C.A., Li J.H., Delman D., Graham K., Gladney W.L., Hua X., Gao M., Liu D., Borad M.J., Ramanathan R.K., Carpenter E.L., Ji A., de Beer M.C., de Beer F.C., Webb N.R., and G.L. Beatty: Hepatocytes direct the formation of a pro-metastatic niche in the liver Nature 567 (7747): 249-252,2019.
Xu, J., Sai, H., Li, Y., Jordan, A.C., McGettigan, S.E., Chen, J-H., Bedoya, F., Fraietta, J.A., Gladney, W.L., Melenhorst, J.J., and G.L. Beatty: Peripheral blood T cell fitness is diminished in patients with pancreatic carcinoma but can be improved with homeostatic cytokines Cell Mol Gastroenterol Hepatol : 2019.
Liu M, O'Connor RS, Trefely S, Graham K, Snyder NW, Beatty GL.: Metabolic rewiring of macrophages by CpG potentiates clearance of cancer cells and overcomes tumor-expressed CD47-mediated 'don't eat me signal' Nat Immunol 20 (3): 265-275,2019.
Beatty GL, O'Hara MH, Lacey SF, Torigian DA, Nazimuddin F, Chen F, Kulikovskaya IM, Soulen MC, McGarvey M, Nelson AM, Gladney WL, Levine BL, Melenhorst JJ, Plesa G, June CH.: Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology 155 (1): 29-32,2018.
Long KB, Gladney WL, Tooker GM, Graham K, Fraietta JA, Beatty GL.: IFNγ and CCL2 Cooperate to Redirect Tumor-Infiltrating Monocytes to Degrade Fibrosis and Enhance Chemotherapy Efficacy in Pancreatic Carcinoma. Cancer Discov 6 (4): 400-413,2016.
Beatty GL, Gladney WL.: Immune escape mechanisms as a guide for cancer immunotherapy Clin Cancer Res 21 (4): 687,2015.
Beatty GL, Winograd R, Evans RA, Long KB, Luque SL, Lee JW, Clendenin C, Gladney WL, Knoblock DM, Guirnalda PD, Vonderheide RH.: Exclusion of T Cells From Pancreatic Carcinomas in Mice Is Regulated by Ly6C(low) F4/80(+) Extratumoral Macrophages. Gastroenterology 149 (1): 201-10,2015.
Beatty, GL., Torigian, DA., Chiorean EG, Saboury B, Brothers, A., Alavi A. Troxel, AB, Sun W, Teitelbaum UR, Vonderheide RH, PJ O'Dwyer: A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma Clin Cancer Res. 19 (22): 6286-95,2015.
Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun WJ, Huhn RD, Song WR, Li DG, Sharp LL, Torigian DA, O'Dwyer PJ, Vonderheide RH: CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans. Science 331 (6024): 1612-1616,2011.
Academic Contact Information
University of Pennsylvania Perelman School of Medicine
Perelman Center for Advanced Medicine
South Pavilion, Rm 8-107
3400 Civic Center Blvd
Patient appointments: 800-789-7366