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

CH Ottensmeier, KL Perry, EL Harden, J Stasakova… - Cancer research, 2016 - AACR
CH Ottensmeier, KL Perry, EL Harden, J Stasakova, V Jenei, J Fleming, O Wood, J Woo…
Cancer research, 2016AACR
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 …
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.
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