Improving Cancer Immunotherapy through Metabolic Modulation

2020 Emerging Leader Award

Greg Delgoffe, PhD, The University of Pittsburgh

Greg Delgoffe, PhD

Dr. Delgoffe is exploring ways to improve the metabolic function of T cells used in cell-based immunotherapies. The tumor microenvironment (TME) puts T cells under severe metabolic stress, limiting their ability to sustain a prolonged antitumor immune response. Researchers in the Delgoffe laboratory will enhance the quality and efficacy of therapeutic T cells either by making alterations to the cell production process that will increase metabolic health or by genetically engineering the cells to better adapt to and function in the metabolically challenging TME. Dr. Delgoffe received his BS from Western Michigan University before completing PhD training at Johns Hopkins University School of Medicine. After postdoctoral training at St. Jude Children’s Research Hospital, he began his own research group in 2014. His laboratory studies how T cells meet their energetic needs in metabolically challenging microenvironments, especially those found within solid tumors. Dr. Delgoffe works to understand the metabolic demands associated with cancer immunotherapy and develops strategies to bolster the immune system to combat malignancy.

published research

Scharping NE, Rivadeneira DB, Menk AV, Vignali PDA, Ford BR, Rittenhouse NL, Peralta R, Wang Y, Wang Y, DePeaux K, Poholek AC, Delgoffe GM. Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion. Nat Immunol. 2021.

Watson MJ, Vignali PDA, Mullett SJ, Overacre-Delgoffe AE, Peralta RM, Grebinoski S, Menk AV, Rittenhouse NL, DePeaux K, Whetstone RD, Vignali DAA, Hand TW, Poholek AC, Morrison BM, Rothstein JD, Wendell SG, Delgoffe GM. Metabolic support of tumour-infiltrating regulatory T cells by lactic acid. Nature. 2021.

DePeaux K, Delgoffe GM. Metabolic barriers to cancer immunotherapy. Nat Rev Immunol. 2021.

Ford BR, Vignali PDA, Rittenhouse NL, Scharping NE, Peralta R, Lontos K, Frisch AT, Delgoffe GM, Poholek AC. Tumor microenvironmental signals reshape chromatin landscapes to limit the functional potential of exhausted T cells. Sci Immunol. 2022.

Lontos K, Wang Y, Colbert M, Kumar A, Joshi S, Philbin M, Wang Y, Frisch A, Lohmueller J, Rivadeneira DB, Delgoffe GM. Fully murine CD105-targeted CAR-T cells provide an immunocompetent model for CAR-T cell biology. Oncoimmunology. 2022.

Vignali PDA, DePeaux K, Watson MJ, Ye C, Ford BR, Lontos K, McGaa NK, Scharping NE, Menk AV, Robson SC, Poholek AC, Rivadeneira DB, Delgoffe GM. Hypoxia drives CD39-dependent suppressor function in exhausted T cells to limit antitumor immunity. Nat Immunol. 2022.

Lontos K, Wang Y, Joshi SK, Frisch AT, Watson MJ, Kumar A, Menk AV, Wang Y, Cumberland R, Lohmueller J, Carrizosa E, Boyerinas B, Delgoffe GM. Metabolic reprogramming via an engineered PGC-1α improves human chimeric antigen receptor T-cell therapy against solid tumors. J Immunother Cancer. 2023.

DePeaux K, Rivadeneira DB, Lontos K, Dean VG, Gunn WG, Watson MJ, Yao T, Wilfahrt D, Hinck C, Wieteska L, Thorne SH, Hinck AP, Delgoffe GM. An oncolytic virus-delivered TGFβ inhibitor overcomes the immunosuppressive tumor microenvironment. J Exp Med. 2023.