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Figure S2 from Upregulated Glucose Metabolism Correlates Inversely with CD8⁺ T-cell Infiltration and Survival in Squamous Cell Carcinoma

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posted on 2023-03-31, 00:11 authored by Christian H. Ottensmeier, Kate L. Perry, Elena L. Harden, Jana Stasakova, Veronika Jenei, Jason Fleming, Oliver Wood, Jeongmin Woo, Christopher H. Woelk, Gareth J. Thomas, Stephen M. Thirdborough

Figure S2. Analysis of gene coexpression and eigengene relationships with overall survival. (A) Box-and-whisker plots of the Pearson correlation between a module gene's expression profile and the deviance residual, a measure of observed minus expected hazard from a univariate Cox PH model. Horizontal lines represent the median and interquartile ranges. The p-values were calculated using a two-tailed Wilcoxon signed-rank test (p<0.001 versus corDeviance= 0). A positive corDeviance value indicates a shorter than expected survival time whereas a negative value indicates that the observed death came after the model prediction. (B) Network graph where each node is labelled by color according to Pearson correlation between the expected hazard (deviance residual) with each gene's expression profile. Red and blue colors show genes associated with shorter and longer survival times, respectively.

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ARTICLE 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.