title: Upregulated Glucose Metabolism Correlates Inversely with CD8+ T-cell Infiltration and Survival in Squamous Cell Carcinoma.
abstract: Antibodies that block T-cell-regulatory checkpoints have recently emerged as a transformative approach to cancer treatment. However, the clinical efficacy of checkpoint blockade depends upon inherent tumor immunogenicity, with variation in infiltrating T cells contributing to differences in objective response rates. Here, we sought to understand the molecular correlates of tumor-infiltrating T lymphocytes (TIL) in squamous cell carcinoma (SCC), using a systems biologic approach to integrate publicly available omics datasets with histopathologic features. We provide evidence that links TIL abundance and therapeutic outcome to the regulation of tumor glycolysis by EGFR and HIF, both of which are attractive molecular targets for use in combination with immunotherapeutics. Cancer Res; 76(14); 4136-48. ©2016 AACR.
authors.affiliation: Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Christian H
authors.initials: CH
authors.lastname: Ottensmeier
authors.affiliation: Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Perry
authors.affiliation: Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Elena L
authors.initials: EL
authors.lastname: Harden
authors.affiliation: Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Jana
authors.initials: J
authors.lastname: Stasakova
authors.affiliation: Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Veronika
authors.initials: V
authors.lastname: Jenei
authors.affiliation: Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Jason
authors.initials: J
authors.lastname: Fleming
authors.affiliation: Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Oliver
authors.initials: O
authors.lastname: Wood
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton Medicine, Southampton, United Kingdom.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Woo
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton Medicine, Southampton, United Kingdom.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Woelk
authors.affiliation: Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Thomas
authors.affiliation: Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom. s.m.thirdborough@soton.ac.uk.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Thirdborough
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000032:analysis; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000077195:Squamous Cell Carcinoma of Head and Neck; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D051272:Glucose Transporter Type 1; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C495678:Slc2a1 protein, mouse; D066246:ErbB Receptors; D005947:Glucose