Response to immune checkpoint blockade improved in pre-clinical model of breast cancer after bariatric surgery

Bariatric surgery is becoming more prevalent as a sustainable weight loss
approach, with vertical sleeve gastrectomy (VSG) being the first line of
surgical intervention. We and others have shown that obesity exacerbates
tumor growth while diet-induced weight loss impairs obesity-driven
progression. It remains unknown how bariatric surgery-induced weight loss
impacts cancer progression or alters responses to therapy. Using a
pre-clinical model of diet induced obesity followed by VSG or diet-induced
weight loss, breast cancer progression and immune checkpoint blockade
therapy was investigated. Weight loss by bariatric surgery or weight
matched dietary intervention before tumor engraftment protected against
obesity-exacerbated tumor progression. However, VSG was not as effective
as dietary intervention in reducing tumor burden despite achieving similar
extent of weight and adiposity loss. Circulating leptin did not associate
with changes in tumor burden. Uniquely, tumors in mice that received VSG
displayed elevated inflammation and checkpoint ligand PD-L1. Further, mice
that received VSG had reduced tumor infiltrating T lymphocytes suggesting
an ineffective anti-tumor microenvironment. VSG-associated elevation of
PD-L1 prompted us to next investigate the efficacy of immune checkpoint
inhibitors in lean, obese, and formerly obese mice that lost weight by VSG
or weight matched controls. While obese mice were resistant to
immunotherapy, anti-PD-L1 potently impaired tumor progression after VSG
through improved anti-tumor immunity. Thus, in formerly obese mice,
surgical weight loss followed by immunotherapy reduced breast cancer
burden. Further studies are necessary to determine how bariatric surgery
sensitizes tumors to immune checkpoint inhibition.