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

作者: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*
来源:Cancer Research, 2016, 76(14): 4136-4148.
DOI:10.1158/0008-5472.CAN-15-3121

摘要

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.

  • 出版日期2016-7-15