Abstract 1361: Severe hyperglycemia and hyperlipidemia alters tumor growth and immune profiles in syngeneic tumor models
Authors: Hao Sun, Ying Zheng, Ryan Strauch, Yi Zhang, Minqi Huang, Luke Tsai
Journal: Cancer Research (2025)

Background and Objective: The global prevalence of obesity is increasing rapidly, causing the rise of obesity-associated diseases, such as diabetes and cancers. It has been established that obesity increases the risks for various types of cancers. Over the past decades, studies have proposed that obesity promotes cancer progression through mechanisms like chronic low-grade inflammation, which alters immune responses and the tumor microenvironment, ultimately affecting tumor response to therapies. Previous studies in diet induced obese models showed T cells in the colorectal cancer are reduced in obesity. However, it is not clear how the tumor microenvironment is changed under both severe hyperglycemia and hyperlipidemia in different types of cancers. This poster will highlight the changes of immune cell population in syngeneic tumor bearing mice with various cancer types in genetic obese models characterized by severe hyperglycemia and hyperlipidemia. Our study provides a detailed comparisons of how severe hyperglycemia and hyperlipidemia change the immune cells populations and tumor microenvironment in cancer. Notably, these changes observed in different cancer models provide insights into why the risk of various cancer types increases differently under conditions of severe obesity. In addition, we also provide a platform for studies on cancer therapeutics in hyperglycemia and hyperlipidemia mouse models. Method and Result: db/db mice and C57BL/6 mice were fed with normal chow diet or high fat diet were used to examine syngeneic tumor growth kinetics. Changes of immune cells populations in different tissues were evaluated by FACS analysis. Both B16F10 melanoma and MC38 colorectal cancer tumors in db/db mice, with severe hyperglycemia and hyperlipidemia, grew significantly faster comparing to lean mice. Changes immune cells populations were observed in both models but differently. Although increased macrophages population is observed in both models, the obesity resulted changes of activated cytotoxic T cells and activated helper T cells were significant in blood and tumors from MC38 bearing mice but not B16F10 bearing mice. The results indicate that MC38 colorectal cancer exhibits more pronounced immune cell changes under obese conditions. RNAseq analysis in the tumor also revealed altered metabolic pathways and oncology pathways in the db/db mice, consistent with the observed faster tumor growth in db/db mice. Conclusion: Hyperglycemia and hyperlipidemia in obesity promote the tumor growth of many types of cancers. The immune cell population, tumor microenvironment and tumor energy metabolism shift in hyperglycemia and hyperlipidemia condition, leading to an altered tumor growth rate and response to cancer therapies. HD Biosciences, a WuXi AppTec company, provides obese tumor models and have in vivo capability for preclinical cancer drug efficacy study in obese condition. Citation Format: Hao Sun, Ying Zheng, Ryan Strauch, Yi Zhang, Minqi Huang, Luke Tsai. Severe hyperglycemia and hyperlipidemia alters tumor growth and immune profiles in syngeneic tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1361.