Evolution of tumor microenvironment in colorectal liver metastases under treatment stress

Abbreviations: (A) BOR: best overall response; PR: partial response; SD: stable disease; PD: progressive disease; a: KEGG DNA replication; b: GO DNA metabolic process; c: GO Cell cycle; d: GO Cell cycle process; e: GO Glycer ophospholipid metabolic process; f: GO Regulation of insulin like growth factor receptor signaling pathway; g: GO Brown fat cell differentiation; h: GO Positive regulation of lipid storage; i: KEGG Lysine degradation; j, GO Regulation of glucose metabolic process; k, GO Positive regulation of triglyceride metabolic process; l, GO Tetrahydrofolate metabolic process; m, KEGG Fatty acid metabolism; n, GO Fatty acid metabolic process; o, GO Positive regulation of steroid metabolic process; p, GO Positive regulation of fatty acid metabolic process; q, GO Regulation of fatty acid biosynthetic process; r, GO Positive regulation of cellular response to insulin stimulus; s, GO Hemoglobin metabolic process; t, GO Regulation of cellular response to insulin stimulus; u, GO Regulation of insulin receptor signaling pathway; v, GO Amino sugar metabolic process; w, GO Unsaturated fatty acid biosynthetic process; x, GO Antigen processing and presentation; y, GO Cellular response to lipoprotein particle stimulus; z, GO Leukocyte migration; aa, GO Endocytosis; ab, GO Positive regulation of response to stimulus; ac, GO Positive regulation of inflammatory response; ad, GO Regulation of activated T cell proliferation; ae, KEGG JAK STAT signaling pathway; af, GO Adaptive immune response; ag, GO Cytokine metabolic process; ah, KEGG Lysosome; ai, GO Positive regulation of mast cell activation; aj, KEGG Chemokine signaling pathway; ak, GO Leukocyte proliferation; al, GO Regulation of alpha beta T cell differentiation; am, GO Negative regulation of nitric oxide metabolic process; an, KEGG T cell receptor signaling pathway; ao, GO Regulation of B cell proliferation; P: patient; pre: pre-treatment; post: post-treatment. Remarkably, correlation analysis of the TCGA Pan-Cancer data revealed a significant positive correlation between neutrophils and fatty acid metabolism, and a negative correlation between neutrophils and T-cell immunity (Supplementary Figure S5D-E). GSEA and ssGSEA analysis indicated that tumors treated with bevacizumab plus chemotherapy significantly upregulated the interferon response, TNF-α signaling pathways and T-cell receptor signaling pathway (Supplementary Figure S6B-C), suggesting that chemotherapy with bevacizumab promoted tumor T-cell inf