Distinguishing the pros and cons of metabolic reprogramming in oncolytic virus immunotherapy

Oncolytic viruses (OVs) represent a class of cancer immunotherapies that rely on hijacking the host cell factory for replicative oncolysis and eliciting immune responses for tumor clearance. An increasing evidence suggests that the metabolic state of tumor cells and immune cells is a putative determinant of the efficacy of cancer immunotherapy. However, how therapeutic intervention with OVs affects metabolic fluxes within the tumor microenvironment (TME) remains poorly understood. Herein, we review the complexities of metabolic reprogramming involving the effects of viruses and their consequences on tumor cells and immune cells. We highlight the inherent drawback of oncolytic virotherapy, namely that treatment with OVs inevitably further exacerbates the depletion of nutrients and the accumulation of metabolic wastes in the TME, leading to a metabolic barrier to antitumor immune responses. We also describe targeted metabolic strategies that can be used to unlock the therapeutic potential of OVs.

• Publication year

  2022

• Venue

  International Journal of Cancer

• Publication date

  2022-05-27

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1002/ijc.34139PMID 35633046
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Distinguishing the pros and cons of metabolic reprogramming in oncolytic virus immunotherapy Improving identification of symptomatic cancer at primary care clinics: A predictive modeling analysis in Botswana

  2022cited by this paper
• Modulation of Macrophage Immunometabolism: A New Approach to Fight Infections

  2022cited by this paper
• An engineered oncolytic vaccinia virus encoding a single-chain variable fragment against TIGIT induces effective antitumor immunity and synergizes with PD-1 or LAG-3 blockade

  2021cited by this paper
• Newcastle disease virus degrades SIRT3 via PINK1-PRKN-dependent mitophagy to reprogram energy metabolism in infected cells

  2021cited by this paper
• Lipid signalling enforces Treg cell functional specialization in tumours

  2021cited by this paper
• Metabolic barriers to cancer immunotherapy

  2021influential reference
• Enhanced antitumor efficacy of a novel oncolytic vaccinia virus encoding a fully monoclonal antibody against T-cell immunoglobulin and ITIM domain (TIGIT)

  2021cited by this paper
• Modulating glutamine metabolism to control viral immuno-inflammatory lesions.

  2021cited by this paper
• Suppression of innate immune signaling molecule, MAVS, reduces radiation-induced bystander effect

  2020cited by this paper
• Consequences of Metabolic Interactions during Staphylococcus aureus Infection

  2020cited by this paper
• Targeting Metabolic Plasticity and Flexibility Dynamics for Cancer Therapy.

  2020cited by this paper
• Enhanced Lipid Accumulation and Metabolism Are Required for the Differentiation and Activation of Tumor-Associated Macrophages

  2020cited by this paper
• STING pathway expression identifies non-small cell lung cancers with an immune-responsive phenotype.

  2020cited by this paper
• Recent advances of oncolytic virus in cancer therapy

  2020cited by this paper
• Tumor localization of oncolytic adenovirus assisted by pH-degradable microgels with JQ1-mediated boosting replication and PD-L1 suppression for enhanced cancer therapy.

  2020cited by this paper
• Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

  2020cited by this paper
• Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis

  2020cited by this paper
• Sculpting tumor microenvironment with immune system: from immunometabolism to immunoediting

  2019cited by this paper
• Metabolic interventions in the immune response to cancer

  2019cited by this paper
• Oncolytic Viruses Engineered to Enforce Leptin Expression, Reprogram Tumor-Infiltrating T Cell Metabolism, and Promote Tumor Clearance.

  2019cited by this paper
• Recombinant Adenovirus Expressing a Soluble Fusion Protein PD-1/CD137L Subverts the Suppression of CD8+ T Cells in HCC.

  2019cited by this paper
• Immunity, Hypoxia and Metabolism - the ménage à trois of cancer: implications for immunotherapy.

  2019cited by this paper
• Metabolic coordination of T cell quiescence and activation

  2019cited by this paper
• Viral hijacking of cellular metabolism

  2019cited by this paper
• Dendritic Cell Metabolism and Function in Tumors.

  2019cited by this paper
• Macrophages and Metabolism in the Tumor Microenvironment.

  2019cited by this paper
• Inhibition of pyruvate dehydrogenase kinase enhances the antitumor efficacy of oncolytic reovirus.

  2019cited by this paper
• Virus Control of Cell Metabolism for Replication and Evasion of Host Immune Responses

  2019cited by this paper
• Membrane Cholesterol Efflux Drives Tumor-Associated Macrophage Reprogramming and Tumor Progression.

  2019cited by this paper
• Glycolysis Is an Intrinsic Factor for Optimal Replication of a Norovirus

  2019cited by this paper
• Targeting aerobic glycolysis by dichloroacetate improves Newcastle disease virus-mediated viro-immunotherapy in hepatocellular carcinoma

  2019influential reference
• Glutaminolysis and Glycolysis Are Essential for Optimal Replication of Marek’s Disease Virus

  2019cited by this paper
• The Acidic Tumor Microenvironment as a Driver of Cancer.

  2019cited by this paper
• Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion

  2019cited by this paper
• Molecular signatures associated with prostate cancer cell line (PC-3) exposure to inactivated Zika virus

  2019cited by this paper
• The Metabolic Profile of Tumor and Virally Infected Cells Shapes Their Microenvironment Counteracting T Cell Immunity

  2019cited by this paper
• 2-Deoxyglucose and Newcastle Disease Virus Synergize to Kill Breast Cancer Cells by Inhibition of Glycolysis Pathway Through Glyceraldehyde3-Phosphate Downregulation

  2019cited by this paper
• NK Cell Metabolism and Tumor Microenvironment

  2019cited by this paper
• Metabolic Control of CD8+ T Cell Fate Decisions and Antitumor Immunity.

  2018cited by this paper
• The Immune Landscape of Cancer.

  2018cited by this paper
• Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression

  2018cited by this paper
• Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism.

  2018cited by this paper
• Multidimensional analyses reveal distinct immune microenvironment in hepatitis B virus-related hepatocellular carcinoma

  2018cited by this paper
• Complex lipid metabolic remodeling is required for efficient hepatitis C virus replication.

  2018cited by this paper
• Antagonism of Glycolysis and Reductive Carboxylation of Glutamine Potentiates Activity of Oncolytic Adenoviruses in Cancer Cells.

  2018influential reference
• Metformin induces CD11b+-cell-mediated growth inhibition of an osteosarcoma: implications for metabolic reprogramming of myeloid cells and anti-tumor effects

  2018cited by this paper
• Lactate-Mediated Acidification of Tumor Microenvironment Induces Apoptosis of Liver-Resident NK Cells in Colorectal Liver Metastasis

  2018cited by this paper
• Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship.

  2018cited by this paper
• Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade

  2018cited by this paper
• Hepatitis C virus infection triggers a tumor‐like glutamine metabolism

  2017cited by this paper
• Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments.

  2017cited by this paper
• Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy.

  2017cited by this paper
• Viral MicroRNAs Repress the Cholesterol Pathway, and 25-Hydroxycholesterol Inhibits Infection

  2017cited by this paper
• Interplay between Immune Checkpoint Proteins and Cellular Metabolism.

  2017cited by this paper
• Metabolic Instruction of Immunity.

  2017cited by this paper
• PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target

  2017cited by this paper
• Energy metabolic pathways control the fate and function of myeloid immune cells

  2017cited by this paper
• Designing and building oncolytic viruses

  2017cited by this paper
• Lipids, lipid metabolism and Kaposi’s sarcoma-associated herpesvirus pathogenesis

  2017cited by this paper
• Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the Inhibitory Receptor PD-1 Are an Early Driver of CD8(+) T Cell Exhaustion.

  2016cited by this paper
• L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity

  2016cited by this paper
• The Emerging Hallmarks of Cancer Metabolism.

  2016cited by this paper
• Vaccinia Virus Immunomodulator A46: A Lipid and Protein-Binding Scaffold for Sequestering Host TIR-Domain Proteins

  2016cited by this paper
• LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells.

  2016cited by this paper
• mTORC1 and mTORC2 in cancer and the tumor microenvironment

  2016cited by this paper
• Vesicular stomatitis virus is a potent agent for the treatment of malignant ascites.

  2016cited by this paper
• Metabolic Reprogramming of Immune Cells in Cancer Progression.

  2015cited by this paper
• Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity

  2015cited by this paper
• The Kaposi's Sarcoma-Associated Herpesvirus (KSHV)-Induced 5-Lipoxygenase-Leukotriene B4 Cascade Plays Key Roles in KSHV Latency, Monocyte Recruitment, and Lipogenesis

  2014cited by this paper
• Cellular targets for improved manufacturing of virus-based biopharmaceuticals in animal cells.

  2014cited by this paper
• Metabolism of stromal and immune cells in health and disease

  2014cited by this paper
• Triggering unfolded protein response by 2-Deoxy-d-glucose inhibits porcine epidemic diarrhea virus propagation

  2014cited by this paper
• Beta Interferon Regulation of Glucose Metabolism Is PI3K/Akt Dependent and Important for Antiviral Activity against Coxsackievirus B3

  2014cited by this paper
• Dichloroacetate blocks aerobic glycolytic adaptation to attenuated measles virus and promotes viral replication leading to enhanced oncolysis in glioblastoma

  2014cited by this paper
• From Scourge to Cure: Tumour-Selective Viral Pathogenesis as a New Strategy against Cancer

  2014cited by this paper
• Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication.

  2014cited by this paper
• Functional polarization of tumour-associated macrophages by tumour-derived lactic acid

  2014cited by this paper
• The Kaposi's Sarcoma-Associated Herpesvirus (KSHV)-Induced 5-Lipoxygenase-Leukotriene B4 Cascade Plays Key Roles in KSHV Latency, Monocyte Recruitment, and Lipogenesis

  2013cited by this paper
• Metabolic pathways recruited in the production of a recombinant enveloped virus: mining targets for process and cell engineering.

  2013cited by this paper
• Posttranscriptional control of T cell effector function by aerobic glycolysis.

  2013cited by this paper
• A mechanism for induction of a hypoxic response by vaccinia virus

  2013cited by this paper
• Mitochondrial-mediated antiviral immunity.

  2013cited by this paper
• Argininosuccinate synthetase 1 depletion produces a metabolic state conducive to herpes simplex virus 1 infection

  2013cited by this paper
• PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells

  2012cited by this paper
• c-Cbl-Mediated Selective Virus-Receptor Translocations into Lipid Rafts Regulate Productive Kaposi's Sarcoma-Associated Herpesvirus Infection in Endothelial Cells

  2011cited by this paper
• The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status

  2010cited by this paper
• Dichloroacetate (DCA) enhances tumor cell death in combination with oncolytic adenovirus armed with MDA-7/IL-24

  2010cited by this paper
• Bidirectional transport of amino acids regulates mTOR and autophagy.

  2009cited by this paper
• Relationship between 31P metabolites and oncolytic viral therapy sensitivity in human colorectal cancer xenografts

  2009cited by this paper
• Down-regulation of multiple cell survival proteins in head and neck cancer cells by an apoptogenic mutant of adenovirus type 5.

  2009cited by this paper
• Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction

  2008cited by this paper
• Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase

  2008cited by this paper
• Hypoxia, HIF1 and glucose metabolism in the solid tumour

  2008cited by this paper
• Lipid Rafts of Primary Endothelial Cells Are Essential for Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8-Induced Phosphatidylinositol 3-Kinase and RhoA-GTPases Critical for Microtubule Dynamics and Nuclear Delivery of Viral DNA but Dispensable for Binding and Entry

  2007cited by this paper
• Inhibitory effect of tumor cell-derived lactic acid on human T cells.

  2007cited by this paper
• History of oncolytic viruses: genesis to genetic engineering.

  2007cited by this paper
• Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses

  2006cited by this paper
• Oncolytic Virotherapy Synergism with Signaling Inhibitors: Rapamycin Increases Myxoma Virus Tropism for Human Tumor Cells

  2006cited by this paper
• HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia.

  2006cited by this paper
• VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents.

  2003cited by this paper

• Synergistic anti-tumor effects of oncolytic virus and anti-programmed cell death protein 1 antibody combination therapy: For suppression of lymph node and distant metastasis in a murine melanoma model.

  2024cites this paper