GSE174761
Bariatric surgery reduces obesity associated breast cancer and enhances response to immunotherapy [Tumor - breast cancer RNA-seq]
Patients undergoing bariatric surgery are protected from subsequent breast cancer risk. It is unknown whether weight loss alone or surgery-specific alterations mediate risk reduction. We examined breast cancer in a pre-clinical model of diet induced obesity (DIO) followed by vertical sleeve gastrectomy (VSG) or dietary weight loss. DIO exacerbated tumor progression compared to lean controls, while VSG-induced weight loss reversed this exacerbation. However, dietary interventions were more effective than VSG despite similar reductions in weight and adiposity, potentially due to elevated immunosuppression after VSG. In tumor bearing mice, anti-PD-L1 immunotherapy after VSG improved anti-tumor immunity and potently impaired tumor progression. Thus, weight loss before tumor onset was protective regardless of intervention. Importantly, immunotherapy specifically improved outcomes in VSG. Overall design: RNA-seq data from bulk tumors (orthotopically injected E0771 breast cancer). Female C57BL/6J mice were weaned onto low fat diet (LFD) to remain lean or onto obesogenic high fat diet (HFD) to become obese. After 16 weeks on diet, HFD fed mice displayed marked obesity (Diet Induced Obesity, DIO). DIO mice then underwent surgical or dietary weight loss interventions. 5 Mouse cohorts: 1) Mice were that were lean mice fed low fat diet (LFD), 2) DIO mice fed obesogenic high fat diet (HFD), or mice that lost weight in 3 ways: 4) formerly obese mice receiving bariatric surgery (Vertical sleeve gastrectomy), 5) formerly obese mice with diet switch (DS) from HFD to LFD, or 6) formerly obese mice with caloric restriction (CR) to match weight loss in VSG cohort. All mice not receiving VSG had a sham surgery as a control.  E0771 syngeneic breast cancer cells were orthotopically implanted into the 4th mammary fat pad two weeks following surgical or dietary weight loss interventions, when weight loss was stabilized.