Project description:Examination of transcriptional changes associated with diet-induced obesity in tumor-infiltrating CD45+ leukocytes from syngeneic MC38 colorectal tumors.
Project description:Multiple cancers, including colorectal cancer (CRC), are more frequent and often more aggressive in obese individuals. Here, we show that macrophages accumulate within tumors of obese CRC patients and in obese CRC mice and promote accelerated tumor growth. These changes are initiated by oleic acid accumulation and subsequent tumor cell-derived acid production, and driven by signaling through GPR65, an acid-sensing receptor on CRC-associated macrophages. We demonstrate a similar role for GPR65 in hepatocellular carcinoma (HCC) in obese mice. Tumors in obese patients with CRC or HCC also exhibit increased GPR65 expression, suggesting that the mechanism revealed here likely contributes to tumor growth in a range of obesity-associated cancers and represents a potential therapeutic target.
Project description:Examination of transcriptional changes associated with diet-induced obesity in CD8+ T lymphocytes that infiltrate syngeneic MC38 tumors.