title: Cytokines and metabolic factors regulate tumoricidal T-cell function during cancer immunotherapy.
abstract: Recent advances in cancer biology and genetics have fostered precision therapies targeting tumor-specific attributes. Immune-based therapies that elicit cytolytic T cells (CTL) specific for tumor antigens can provide therapeutic benefit to cancer patients, however, cure rates are typically low. This largely results from immunosuppressive mechanisms operating within the tumor microenvironment, many of which inflict metabolic stresses upon CTL. Conversely, immunotherapies can mitigate specific metabolic stressors. For instance, dual costimulation immunotherapy with CD134 (OX40) plus CD137 (4-1BB) agonists appears to mediate tumor control in part by engaging cytokine networks that enable infiltrating CTL to compete for limiting supplies of glucose. Future efforts combining modalities that endow CTL with complimentary metabolic advantages should improve therapeutic efficacies.
authors.affiliation: Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.|Department of Medicine, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Adler
authors.affiliation: Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Mittal
authors.affiliation: Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Ryan
authors.affiliation: Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
authors.forename: Beiyan
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Wasser
authors.affiliation: Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Vella
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002465:Cell Movement; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005947:Glucose / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D053262:Receptors, OX40 / Q000819:agonists; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation; D019139:Tumor Escape; D059016:Tumor Microenvironment; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000819:agonists
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D053262:Receptors, OX40; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D005947:Glucose
keywords: T cells; costimulation; immunotherapy