Gregory L. Beatty, MD, PhD
Professor of Medicine (Hematology-Oncology)
Department: Medicine
Graduate Group Affiliations
Contact information
Perelman Center for Advanced Medicine
South Pavilion, Rm 8-107
3400 Civic Center Blvd
Philadelphia, PA 19104-5156
South Pavilion, Rm 8-107
3400 Civic Center Blvd
Philadelphia, PA 19104-5156
Education:
BS
Bucknell University, 1995.
PhD
University of Pennsylvania, 2000.
MD
University of Pennsylvania, 2004.
Permanent linkBS
Bucknell University, 1995.
PhD
University of Pennsylvania, 2000.
MD
University of Pennsylvania, 2004.
Description of Research Expertise
My laboratory integrates basic science and clinical research to investigate the role of innate and adaptive immunity—particularly monocytes, macrophages, and T cells—in regulating tumor biology in pancreatic and other gastrointestinal cancers. We also study malignancies like glioblastoma, which have shown limited success with immunotherapy. We hypothesize that these immune cells are key regulators of tumor progression and therapeutic outcomes.Clinically, we analyze patient-derived samples to understand how macrophage and T cell biology influences metastatic disease and the efficacy of therapies. Preclinically, we use genetically engineered mouse models alongside advanced tissue imaging techniques, specifically multiplex immunohistochemistry, to study the dynamics of macrophages and T cells within the tumor microenvironment. This platform supports detailed mechanistic studies of immune interactions as well as rapid evaluation of novel immunotherapies.
Our research areas include:
1. signaling pathways driving cross-talk between macrophages, T cells, and tumor cells in vivo,
2. contributions of hematopoietic and non-hematopoietic cells in shaping immune cell function within tumors,
3. trafficking and localization of macrophages and T cells to primary and metastatic sites,
4. strategies to harness both macrophages and T cells for effective anti-tumor immunity, and
5. impacts of chemotherapy and radiation on immune cell biology within tumors.
Selected Publications
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, Nov 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, Mar 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 8(4): 656-658, 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, Mar 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, Jul 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, Apr 2016.
Beatty GL, Gladney WL.: Immune escape mechanisms as a guide for cancer immunotherapy. Clin Cancer Res 21(4): 687, Feb 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, Jul 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, Nov 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, Mar 25 2011.