Upregulated Glucose Metabolism Correlates Inversely with CD8+ T-cell Infiltration and Survival in Squamous Cell Carcinoma

• Published in: Cancer research (Chicago, Ill.) Vol. 76; no. 14; pp. 4136 - 4148
• Main Authors: Ottensmeier, Christian H, Perry, Kate L, Harden, Elena L, Stasakova, Jana, Jenei, Veronika, Fleming, Jason, Wood, Oliver, Woo, Jeongmin, Woelk, Christopher H, Thomas, Gareth J, Thirdborough, Stephen M
• Format: Journal Article
• Language: English
• Published: United States 15.07.2016
• Subjects: Animals; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; CD8-Positive T-Lymphocytes - immunology; ErbB Receptors - genetics; ErbB Receptors - physiology; Female; Glucose - metabolism; Glucose Transporter Type 1 - analysis; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - mortality; Hypoxia-Inducible Factor 1, alpha Subunit - physiology; Lymphocytes, Tumor-Infiltrating - immunology; Mice; Mice, Inbred C57BL; Squamous Cell Carcinoma of Head and Neck; Transcriptome; Up-Regulation
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-15-3121

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.