Obesity reprograms bone marrow derived macrophages to promote anti-tumor immunity 3689

Abstract Description Obesity has been identified as the number two modifiable risk factor for cancer, behind only smoking. This prolonged exposure to excessive nutrients and altered systemic metabolism can promote a distinct immunosuppressive state for tumor immunosurveillance. Obesity has also shown to have a detrimental effect on bone homeostasis by altering bone marrow and hematopoietic stem cell differentiation by shifting stem cells in favor of myeloid progenitors. Further these obesity-induced changes in the bone marrow can lead to dramatic bone marrow remodeling, compromising immune cell functions, which can impact host response to inflammatory diseases and regulation of systemic metabolism. Interestingly, we found that bone marrow derived macrophages (BMDMs) taken from obese (HFD) mice maintain an altered metabolic phenotype, exhibiting increased basal OCR and ECAR compared to BMDMs from lean mice. Additionally, HFD BMDMs exhibited increased mitochondrial ROS, increased lipid uptake and increased pro-inflammatory markers such as MHCII and CD86. Transplanted bone marrow from obese mice into irradiated lean mice resulted in significantly reduced tumor size when subcutaneously injected with MC38 tumor cells. Further, mice that received HFD bone marrow exhibited increased macrophages and CD8 T cell infiltration into tumors. Together these data suggest that an “innate memory” of obesity is preserved in the bone marrow which can impact subsequent anti-tumor immunity and tumor growth. Funding Sources K00CA234920 (JEB) Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)