Macrophage M2 Co-expression Factors Correlate With the Immune Microenvironment and Predict Outcome of Renal Clear Cell Carcinoma

Abstract

Purpose: In the tumor microenvironment, the functional differences among various tumor-associated macrophages (TAM) are not completely clear. Tumor-associated macrophages are thought to promote the progression of cancer. This article focuses on exploring M2 macrophage-related factors and behaviors of renal clear cell carcinoma.Method: We obtained renal clear cell carcinoma data from TCGA-KIRC-FPKM, GSE8050, GSE12606, GSE14762, and GSE3689. We used the “Cibersort” algorithm to calculate type M2 macrophage proportions among 22 types of immune cells. M2 macrophage-related co-expression module genes were selected using weighted gene co-expression network analysis (WGCNA). A renal clear cell carcinoma prognosis risk score was built based on M2 macrophage-related factors. The ROC curve and Kaplan–Meier analysis were performed to evacuate the risk score in various subgroups. The Pearson test was used to calculate correlations among M2 macrophage-related genes, clinical phenotype, immune phenotype, and tumor mutation burden (TMB). We measured differences in co-expression of genes at the protein level in clear renal cell carcinoma tissues.Results: There were six M2 macrophage co-expressed genes (F13A1, FUCA1, SDCBP, VSIG4, HLA-E, TAP2) related to infiltration of M2 macrophages; these were enriched in neutrophil activation and involved in immune responses, antigen processing, and presentation of exogenous peptide antigen via MHC class I. M2-related factor frequencies were robust biomarkers for predicting the renal clear cell carcinoma patient clinical phenotype and immune microenvironment. The Cox regression model, built based on M2 macrophage-related factors, showed a close prognostic correlation (AUC = 0.78). The M2 macrophage-related prognosis model also performed well in various subgroups. Using western blotting, we found that VSIG4 protein expression levels were higher in clear renal cell carcinoma tissues than in normal tissues.Conclusion: These co-expressed genes were most related to the M2 macrophage phenotype. They correlated with the immune microenvironment and predicted outcomes of renal clear cell carcinoma. These co-expressed genes and the biological processes associated with them might provide the basis for new strategies to intervene via chemotaxis of M2 macrophages.

Oncogenic Vav1-Myo1f induces therapeutically targetable macrophage-rich tumor microenvironment in peripheral T cell lymphoma

“…In this context, it did not escape our attention that mouse Vav1-Myo1f pre-lymphoma samples were specifically enriched in a TAM-associated signature, supporting an early crosstalk between Vav1-Myo1f -expressing CD4 + T cells and the tumor microenvironment implicated in tumor initiation. In human PTCL, the presence of tumor-infiltrating myeloid cells, including TAMs, has been associated with poor prognosis, suppression of anti-tumor responses, and limited response to initial therapy ( Allavena et al, 2021 ; Skytthe et al, 2020 ; Wang et al, 2021 ). Here we show that in vivo depletion of macrophages inhibits Vav1-Myo1f CD4 + lymphoma cell proliferation and survival, demonstrating a close interdependency between lymphoma cells and TAM and supporting a role for TAM-directed targeted therapies for the treatment of this disease.…”

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“…All of these results imply that FUCA1/FUCA2 may be acting in a tumor-suppressive role, and lower expression of FUCA1/FUCA2 prognosticates worse pathological results, less therapeutic effect, and shorter PFI. This finding is consistent with many previous studies, which further validate the reliability of our conclusion (12,13,(21)(22)(23).…”

The Tumor Immune Profile of Murine Ovarian Cancer Models: An Essential Tool for Ovarian Cancer Immunotherapy Research

“…We generated signatures of M0/M1/M2 phenotypes and found that STOSE tumors were enriched with M2 TAMs [F13a1 (27), Fabp5 (28), S100a4 and Arg1 (26); Supplementary Fig. S2; Supplementary Table S5; ref .…”