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. 2021 Jul 6;9(7):e002773. doi: 10.1136/jitc-2021-002773

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© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

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Metformin induced shifts in TIME. (A) Differential gene expression profiles for metformin treated vs untreated control groups presented as volcano plot. The log2 fold changes and their cut-offs for adjusted p values are shown. Highly statistically significant genes fall at the top of the plot above the horizontal lines representing the p value thresholds with highly differentially expressed genes falling on either sides of the plot. Statistically significant genes with a p value below the defined threshold are colored and the 40 most statistically significant genes are labeled in the plot. Metformin treated tumors demonstrated a high density of statistically significant upregulated genes with only a very few statistically significant downregulated genes. (B) Heatmap of the upregulated and downregulated gene sets/pathways. (C) Heatmap of the different immune cell types within the tumor microenvironment. DC, dendritic cell; TIME, tumor immune microenvironment; TIL, tumor infiltrating lymphocyte.