Abstract While advances in immunotherapy have improved treatment of breast cancer, many patients do not respond to current immunotherapies, there is not a reliable predictor of immunotherapy efficacy, and responders may develop resistance to immunotherapies. Additionally, obese breast cancer patients have advanced disease at diagnosis, differential responses to therapies, and worsened prognoses. As obesity has become a worldwide epidemic, understanding how obese patients develop breast cancer and respond to therapeutics is of critical importance. One emerging field of treatment in immune oncology is the use of cancer vaccines that stimulate the patient’s immune system against an antigen expressed on tumors. Obesity within the context of infectious diseases has been shown to cause diminished vaccine-induced immune responses. However, there is a significant gap in our understanding of how obesity impacts vaccination efficacy in the context of cancer. Our group has previously published the use of a pre-clinical therapeutic vaccine targeting HER2 in combination with a checkpoint inhibitor. Using this therapeutic, we hypothesized that obesity would reduce the efficacy of therapeutic vaccination. We used our published model of spontaneous breast cancer driven by expression of a HER2 isoform to investigate the impact of obesity on therapeutic vaccination. On a high fat diet, mice gain significantly more weight and have significantly higher serum leptin levels than their low fat diet counterparts. Obese mice also have a longer time to both tumor formation and tumor endpoint. Importantly, therapeutic vaccination early after tumor detection completely protects lean mice from tumor development, while only 30% of obese mice are protected from tumor development. Early analysis suggests obesity skews immune memory both locally and systemically. It is critical that we understand the anti-tumor response of obese patients to immunotherapies to effectively treat patients. Citation Format: Abigail Jolley, Erika Crosby, Gabrielle Dailey, Jessica Finkler, Christopher Rabiola. Obesity impairs anti-tumor responses to breast cancer vaccination abstract. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr C071.
Jolley et al. (2026) studied this question.