Full Text Journal Articles by
Author Greg M Delgoffe

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Restoring glucose uptake rescues neutrophil dysfunction and protects against systemic fungal infection in mouse models of kidney disease.

Chetan V Jawale, Kritika Ramani, De-Dong Li, Bianca M Coleman, Rohan S Oberoi, Saran Kupul, Li Lin, Jigar V Desai, Greg M Delgoffe, Michail S Lionakis, Filitsa H Bender, Alexander J Prokopienko, Thomas D Nolin, Sarah L Gaffen, Partha S Biswas,

Disseminated candidiasis caused by the fungus Candida albicans is a major clinical problem in individuals with kidney disease and accompanying uremia; disseminated candidiasis fatality is twice as common in patients with uremia as those with normal kidney function. Many antifungal drugs are nephrotoxic, making treatment of these patients particularly challenging. ... Read more >>

Sci Transl Med (Science translational medicine)
[2020, 12(548):]

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NFATC4 promotes quiescence and chemotherapy resistance in ovarian cancer.

Alexander J Cole, Mangala Iyengar, Santiago Panesso-Gómez, Patrick O'Hayer, Daniel Chan, Greg M Delgoffe, Katherine M Aird, Euisik Yoon, Shoumei Bai, Ronald J Buckanovich,

Development of chemotherapy resistance is a major problem in ovarian cancer. One understudied mechanism of chemoresistance is the induction of quiescence, a reversible nonproliferative state. Unfortunately, little is known about regulators of quiescence. Here, we identify the master transcription factor nuclear factor of activated T cells cytoplasmic 4 (NFATC4) as ... Read more >>

JCI Insight (JCI insight)
[2020, 5(7):]

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Checkpoint molecules coordinately restrain hyperactivated effector T cells in the tumor microenvironment.

Min Yang, Wenwen Du, Lixian Yi, Shaoxian Wu, Chunyan He, Wensi Zhai, Cuihua Yue, Runzi Sun, Ashley V Menk, Greg M Delgoffe, Jingting Jiang, Binfeng Lu,

The immune checkpoint blockade (ICB) immunotherapy has prolonged overall survival for cancer patients but the response rates are low. The resistance to ICB is likely due to compensatory upregulation of additional immune inhibitory molecules. In this study, we first systematically examined Tim-3 expression in immune cells in mouse tumors and ... Read more >>

Oncoimmunology (Oncoimmunology)
[2020, 9(1):1708064]

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Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis.

Florian J Weisel, Steven J Mullett, Rebecca A Elsner, Ashley V Menk, Nikita Trivedi, Wei Luo, Daniel Wikenheiser, William F Hawse, Maria Chikina, Shuchi Smita, Laura J Conter, Stephen M Joachim, Stacy G Wendell, Michael J Jurczak, Thomas H Winkler, Greg M Delgoffe, Mark J Shlomchik,

Germinal center B cells (GCBCs) are critical for generating long-lived humoral immunity. How GCBCs meet the energetic challenge of rapid proliferation is poorly understood. Dividing lymphocytes typically rely on aerobic glycolysis over oxidative phosphorylation for energy. Here we report that GCBCs are exceptional among proliferating B and T cells, as ... Read more >>

Nat. Immunol. (Nature immunology)
[2020, 21(3):331-342]

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Perspectives in immunotherapy: meeting report from the "Immunotherapy Bridge 2018" (28-29 November, 2018, Naples, Italy).

Paolo A Ascierto, Carlo Bifulco, Luigi Buonaguro, Leisha A Emens, Robert L Ferris, Bernard A Fox, Greg M Delgoffe, Jérôme Galon, Cesare Gridelli, Marco Merlano, Paul Nathan, Kunle Odunsi, Hideho Okada, Chrystal M Paulos, Sandro Pignata, Kurt A Schalper, Stefani Spranger, Giampaolo Tortora, Hassane Zarour, Lisa H Butterfield, Igor Puzanov,

Immunotherapy is now widely established as a potent and effective treatment option across several types of cancer. However, there is increasing recognition that not all patients respond to immunotherapy, focusing attention on the immune contexture of the tumor microenvironment (TME), drivers of the immune response and mechanisms of tumor resistance ... Read more >>

J Immunother Cancer (Journal for immunotherapy of cancer)
[2019, 7(1):332]

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Metabolic Consequences of T-cell Costimulation in Anticancer Immunity.

Alvaro Teijeira, Saray Garasa, Inaki Etxeberria, Maria Gato-Cañas, Ignacio Melero, Greg M Delgoffe,

T-cell functional behavior and performance are closely regulated by nutrient availability and the control of metabolism within the T cell. T cells have distinct energetic and anabolic needs when nascently activated, actively proliferating, in naïveté, or in a resting, memory state. As a consequence, bioenergetics are key for T cells ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2019, 7(10):1564-1569]

Cited: 1 time

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Oncolytic Viruses Engineered to Enforce Leptin Expression Reprogram Tumor-Infiltrating T Cell Metabolism and Promote Tumor Clearance.

Dayana B Rivadeneira, Kristin DePeaux, Yiyang Wang, Aditi Kulkarni, Tracy Tabib, Ashley V Menk, Padmavathi Sampath, Robert Lafyatis, Robert L Ferris, Saumendra N Sarkar, Stephen H Thorne, Greg M Delgoffe,

Immunotherapy can reinvigorate dormant responses to cancer, but response rates remain low. Oncolytic viruses, which replicate in cancer cells, induce tumor lysis and immune priming, but their immune consequences are unclear. We profiled the infiltrate of aggressive melanomas induced by oncolytic Vaccinia virus using RNA sequencing and found substantial remodeling ... Read more >>

Immunity (Immunity)
[2019, 51(3):548-560.e4]

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IRF1 Inhibits Antitumor Immunity through the Upregulation of PD-L1 in the Tumor Cell.

Lulu Shao, Weizhou Hou, Nicole E Scharping, Frank P Vendetti, Rashmi Srivastava, Chandra Nath Roy, Ashley V Menk, Yiyang Wang, Joe-Marc Chauvin, Pooja Karukonda, Stephen H Thorne, Veit Hornung, Hassane M Zarour, Christopher J Bakkenist, Greg M Delgoffe, Saumendra N Sarkar,

Multiple studies have associated the transcription factor IRF1 with tumor-suppressive activities. Here, we report an opposite tumor cell-intrinsic function of IRF1 in promoting tumor growth. IRF1-deficient tumor cells showed reduced tumor growth in MC38 and CT26 colon carcinoma and B16 melanoma mouse models. This reduction in tumor growth was dependent ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2019, 7(8):1258-1266]

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Treg Cells Promote the SREBP1-Dependent Metabolic Fitness of Tumor-Promoting Macrophages via Repression of CD8+ T Cell-Derived Interferon-γ.

Chang Liu, Maria Chikina, Rahul Deshpande, Ashley V Menk, Ting Wang, Tracy Tabib, Erin A Brunazzi, Kate M Vignali, Ming Sun, Donna B Stolz, Robert A Lafyatis, Wei Chen, Greg M Delgoffe, Creg J Workman, Stacy G Wendell, Dario A A Vignali,

Regulatory T (Treg) cells are crucial for immune homeostasis, but they also contribute to tumor immune evasion by promoting a suppressive tumor microenvironment (TME). Mice with Treg cell-restricted Neuropilin-1 deficiency show tumor resistance while maintaining peripheral immune homeostasis, thereby providing a controlled system to interrogate the impact of intratumoral Treg ... Read more >>

Immunity (Immunity)
[2019, 51(2):381-397.e6]

Cited: 3 times

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mTORC2 Deficiency Alters the Metabolic Profile of Conventional Dendritic Cells.

Alicia R Watson, Helong Dai, Yawen Zheng, Ryosuke Nakano, Anastasios D Giannou, Ashley V Menk, Donna B Stolz, Greg M Delgoffe, Angus W Thomson,

In myeloid dendritic cells (DC), deletion of the mechanistic target of rapamycin complex 2 (TORC2) results in an augmented pro-inflammatory phenotype and T cell stimulatory activity; however, the underlying mechanism has not been resolved. Here, we demonstrate that mouse bone marrow-derived TORC2-deficient myeloid DC (TORC2-/- DC) utilize an altered metabolic ... Read more >>

Front Immunol (Frontiers in Immunology)
[2019, 10:1451]

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Tumor-Derived α-Fetoprotein Suppresses Fatty Acid Metabolism and Oxidative Phosphorylation in Dendritic Cells.

Patricia M Santos, Ashley V Menk, Jian Shi, Allan Tsung, Greg M Delgoffe, Lisa H Butterfield,

Cellular metabolism supports immune cell function. Here, we identify a reduction in fatty acid synthesis and mitochondrial metabolism in dendritic cells (DC) due to α-fetoprotein (AFP), a protein secreted by hepatocellular cancer (HCC). DCs cultured in the presence of AFP show reduced expression of the metabolic regulatory molecules SREBP-1 and ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2019, 7(6):1001-1012]

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Lymphocyte Activation Gene-3 Maintains Mitochondrial and Metabolic Quiescence in Naive CD4+ T Cells.

Dana M Previte, Christina P Martins, Erin C O'Connor, Meghan L Marre, Gina M Coudriet, Noah W Beck, Ashley V Menk, Rebecca H Wright, Hubert M Tse, Greg M Delgoffe, Jon D Piganelli,

Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed by CD4+ T cells and tempers their homeostatic expansion. Because CD4+ T cell proliferation is tightly coupled to bioenergetics, we investigate the role of LAG-3 in modulating naive CD4+ T cell metabolism. LAG-3 deficiency enhances the metabolic profile of naive CD4+ T cells by elevating ... Read more >>

Cell Rep (Cell Reports)
[2019, 27(1):129-141.e4]

Cited: 3 times

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The Lysophosphatidylcholine Transporter MFSD2A Is Essential for CD8+ Memory T Cell Maintenance and Secondary Response to Infection.

Ann R Piccirillo, Eric J Hyzny, Lisa Y Beppu, Ashley V Menk, Callen T Wallace, William F Hawse, Heather M Buechel, Bernice H Wong, Juat Chin Foo, Amaury Cazenave-Gassiot, Markus R Wenk, Greg M Delgoffe, Simon C Watkins, David L Silver, Louise M D'Cruz,

Access to nutrients is critical for an effective T cell immune response to infection. Although transporters for sugars and amino acids have previously been described in the context of the CD8+ T cell immune response, the active transport of exogenous fatty acids has remained enigmatic. In this study, we discovered ... Read more >>

J. Immunol. (Journal of immunology (Baltimore, Md. : 1950))
[2019, 203(1):117-126]

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Tumor cell oxidative metabolism as a barrier to PD-1 blockade immunotherapy in melanoma.

Yana G Najjar, Ashley V Menk, Cindy Sander, Uma Rao, Arivarasan Karunamurthy, Roma Bhatia, Shuyan Zhai, John M Kirkwood, Greg M Delgoffe,

The tumor microenvironment presents physical, immunologic, and metabolic barriers to durable immunotherapy responses. We have recently described roles for both T cell metabolic insufficiency as well as tumor hypoxia as inhibitory mechanisms that prevent T cell activity in murine tumors, but whether intratumoral T cell activity or response to immunotherapy ... Read more >>

JCI Insight (JCI insight)
[2019, 4(5):]

Cited: 7 times

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Kidney-infiltrating T cells in murine lupus nephritis are metabolically and functionally exhausted.

Jeremy S Tilstra, Lyndsay Avery, Ashley V Menk, Rachael A Gordon, Shuchi Smita, Lawrence P Kane, Maria Chikina, Greg M Delgoffe, Mark J Shlomchik,

While T cells are important for the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis, little is known about how T cells function after infiltrating the kidney. The current paradigm suggests that kidney-infiltrating T cells (KITs) are activated effector cells contributing to tissue damage and ultimately organ failure. Herein, ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2018, 128(11):4884-4897]

Cited: 5 times

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ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumor activity following radiation.

Frank P Vendetti, Pooja Karukonda, David A Clump, Troy Teo, Ronald Lalonde, Katriana Nugent, Matthew Ballew, Brian F Kiesel, Jan H Beumer, Saumendra N Sarkar, Thomas P Conrads, Mark J O'Connor, Robert L Ferris, Phuoc T Tran, Greg M Delgoffe, Christopher J Bakkenist,

DNA-damaging chemotherapy and radiation therapy are integrated into the treatment paradigm of the majority of cancer patients. Recently, immunotherapy that targets the immunosuppressive interaction between programmed death 1 (PD-1) and its ligand PD-L1 has been approved for malignancies including non-small cell lung cancer, melanoma, and head and neck squamous cell ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2018, 128(9):3926-3940]

Cited: 6 times

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IL-23 and IL-1β Drive Human Th17 Cell Differentiation and Metabolic Reprogramming in Absence of CD28 Costimulation.

Shankar Revu, Jing Wu, Matthew Henkel, Natalie Rittenhouse, Ashley Menk, Greg M Delgoffe, Amanda C Poholek, Mandy J McGeachy,

Th17 cells drive autoimmune disease but also control commensal microbes. A common link among antigens from self-proteins or commensal microbiota is relatively low activation of T cell receptor (TCR) and costimulation signaling. Indeed, strong TCR/CD28 stimulation suppressed Th17 cell differentiation from human naive T cells, but not effector/memory cells. CD28 suppressed the ... Read more >>

Cell Rep (Cell Reports)
[2018, 22(10):2642-2653]

Cited: 15 times

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Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions.

Ashley V Menk, Nicole E Scharping, Rebecca S Moreci, Xue Zeng, Cliff Guy, Sonia Salvatore, Heekyong Bae, Jianxin Xie, Howard A Young, Stacy Gelhaus Wendell, Greg M Delgoffe,

To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, ... Read more >>

Cell Rep (Cell Reports)
[2018, 22(6):1509-1521]

Cited: 26 times

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Antitumor T-cell Reconditioning: Improving Metabolic Fitness for Optimal Cancer Immunotherapy.

Dayana B Rivadeneira, Greg M Delgoffe,

With the rapid rise of immunotherapy for cancer treatment, attention has focused on gaining a better understanding of T-cell biology in the tumor microenvironment. Elucidating the factors underlying changes in their function will allow for the development of new therapeutic strategies that could expand the patient population benefiting from immunotherapy, ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2018, 24(11):2473-2481]

Cited: 2 times

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Interferon-γ Drives Treg Fragility to Promote Anti-tumor Immunity.

Abigail E Overacre-Delgoffe, Maria Chikina, Rebekah E Dadey, Hiroshi Yano, Erin A Brunazzi, Gulidanna Shayan, William Horne, Jessica M Moskovitz, Jay K Kolls, Cindy Sander, Yongli Shuai, Daniel P Normolle, John M Kirkwood, Robert L Ferris, Greg M Delgoffe, Tullia C Bruno, Creg J Workman, Dario A A Vignali,

Regulatory T cells (Tregs) are a barrier to anti-tumor immunity. Neuropilin-1 (Nrp1) is required to maintain intratumoral Treg stability and function but is dispensable for peripheral immune tolerance. Treg-restricted Nrp1 deletion results in profound tumor resistance due to Treg functional fragility. Thus, identifying the basis for Nrp1 dependency and the key ... Read more >>

Cell (Cell)
[2017, 169(6):1130-1141.e11]

Cited: 71 times

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Efficacy of PD-1 Blockade Is Potentiated by Metformin-Induced Reduction of Tumor Hypoxia.

Nicole E Scharping, Ashley V Menk, Ryan D Whetstone, Xue Zeng, Greg M Delgoffe,

Blockade of the coinhibitory checkpoint molecule PD-1 has emerged as an effective treatment for many cancers, resulting in remarkable responses. However, despite successes in the clinic, most patients do not respond to PD-1 blockade. Metabolic dysregulation is a common phenotype in cancer, but both patients and tumors are metabolically heterogeneous. ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2017, 5(1):9-16]

Cited: 48 times

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Suppressive IL-17A+Foxp3+ and ex-Th17 IL-17AnegFoxp3+ Treg cells are a source of tumour-associated Treg cells.

Stephanie Downs-Canner, Sara Berkey, Greg M Delgoffe, Robert P Edwards, Tyler Curiel, Kunle Odunsi, David L Bartlett, Nataša Obermajer,

Th17 and regulatory T (Treg) cells are integral in maintaining immune homeostasis and Th17-Treg imbalance is associated with inflammatory immunosuppression in cancer. Here we show that Th17 cells are a source of tumour-induced Foxp3+ cells. In addition to natural (n)Treg and induced (i)Treg cells that develop from naive precursors, suppressive ... Read more >>

Nat Commun (Nature communications)
[2017, 8:14649]

Cited: 17 times

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Filling the Tank: Keeping Antitumor T Cells Metabolically Fit for the Long Haul.

Greg M Delgoffe,

Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2016, 4(12):1001-1006]

Cited: 6 times

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The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction.

Nicole E Scharping, Ashley V Menk, Rebecca S Moreci, Ryan D Whetstone, Rebekah E Dadey, Simon C Watkins, Robert L Ferris, Greg M Delgoffe,

Immunity (Immunity)
[2016, 45(3):701-703]

Cited: 30 times

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Cutting Edge: Murine Mast Cells Rapidly Modulate Metabolic Pathways Essential for Distinct Effector Functions.

Binh Phong, Lyndsay Avery, Ashley V Menk, Greg M Delgoffe, Lawrence P Kane,

There is growing appreciation that cellular metabolic and bioenergetic pathways do not play merely passive roles in activated leukocytes. Rather, metabolism has important roles in controlling cellular activation, differentiation, survival, and effector function. Much of this work has been performed in T cells; however, there is still very little information ... Read more >>

J. Immunol. (Journal of immunology (Baltimore, Md. : 1950))
[2017, 198(2):640-644]

Cited: 9 times

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