Obesity Influences the Expression of Key Immunomodulators in Normal Human Breast Tissue, Basal-like Breast Cancer Patients, and Cell Lines

SIMPLE SUMMARY: Exploring the connection between lifestyle and the progression and aggressiveness of some cancers has become a widely accepted approach to drug development. Metabolic and secretory functions of adipocytes in the tumor microenvironment have drawn interest to their molecular relevance in some malignancies. Adipocytes promote breast cancer growth and metastasis. Immune-sensing cascades seem to be unsuccessful in efforts to control the spread of abnormal malignant cells. Chemotherapy, radiation therapy, and immunotherapy options alone are not efficient in the maintenance of aggressive TNBC patients. There is still a major push for molecular targets to increase the efficacy of therapy options in combination with immune-response therapies. The molecular mechanism by which adipocytes promote cancer aggressiveness is not fully understood. In this study, we explored the influence of human visceral adipocyte secretory factors on immunosuppressive genes in normal breast tissue, breast cancer patients, and basal-like triple-negative breast cancer cell lines. ABSTRACT: Among the different components of the breast cancer microenvironment are adipocytes, which are mainly composed of differentiated adipocytes and adipose progenitors. The role of obesity in tumor progression has become a key topic in clinical studies, but the mechanics of this are still misunderstood. There is significant evidence of serum amyloid (SAA1), an acute-phase protein, being heavily expressed in inflamed, septic conditions. VTCN1 and VSIR, members of the immunoglobulin family, are key players in T-cell regulation. The present study investigates the differentially expressed genes caused by adipose-conditioned media on the novel triple-negative breast cancer cell lines MDA MB 231 and MDA MB 468. RNA sequencing of adipocyte-conditioned media (ACM)-treated MDA MB 231 and MDA MB 468 cells were analyzed and compared using the gene sequencing enrichment analysis database (GSEA). GSEA was also done on microarray data from obese, non-tumorous breast tissue patients (GSE:33526) to show significantly upregulated immunomodulators. Obesity was also shown to influence gene expression related to immune sensing and evasion in a dataset analysis of basal-like obese patients (GSE:79858). We showed obesity significantly upregulated immunomodulators related to immune suppression in non-tumorous, basal-like patients, as well as in novel basal-like TNBC cell lines.