Obesity promotes cancer growth by enhancing the suppressive activity of intratumoral myeloid cells

Abstract

Abstract Epidemiological evidence suggests that obesity is linked to increased risk of developing several types of cancer. However, the mechanisms underlying this phenomenon remain unknown. Successful growth of cancer cells depends on developing mechanisms to evade host immunosurveillance, particularly within the tumor microenvironment. In the current study, we utilized a high-fat-diet (HFD)-induced obese mouse model to gain mechanistic insight into the effect of obesity on progression of implantable syngeneic tumors. When lean or obese mice were implanted with B16.F1 melanoma or MC38 colon carcinoma, tumor growth was more robust in obese group than lean controls, suggesting that obese conditions promote tumor growth. Multi-color flow cytometric analysis and gene expression profiling were carried out on distinct subpopulations of intratumoral myeloid cells. Tumors of lean mice had higher percentages of myeloid cells compared to obese counterparts with characteristics typical of activated inflammatory macrophages. In contrast, tumors of obese mice had disproportionately higher frequency of myeloid derived suppressor cells (MDSC) with a gene signature suggestive of immunosuppressive potential. These findings highlight the role of metaflammation in tumor growth promotion via the regulation of frequency and activation status of distinct subpopulations of intratumoral myeloid cells.