Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment
Year: 2022
Type: article
Abstract: Contrary to the "obesity paradox," which arises from retrospective studies relying on body mass index to define obesity, epidemiologic evidence suggests central or visceral obesity is associated with a higher risk for the development of lung cancer. About 60% of individuals at high risk for developing lung cancer or those already with early-stage disease are either overweight or obese. Findings from resected patient tumors and mouse lung tumor models show obesity dampens immune activity in the tumor microenvironment (TME) encouraging disease progression. In line with this, we have observed a marked, obesity-specific enhancement in the presence and phenotype of immunosuppressive regulatory T (Treg) cells in murine tumors as well as the airways of both humans and mice. Leveraging direct metabolomic measurements and robust inferred analyses from RNA-sequencing data, we here demonstrate for the first time that visceral adiposity alters the lung microenvironment via dysregulated acetyl-CoA metabolism in a direction that facilitates immune suppression and lung carcinogenesis.
Source: Cancer & Metabolism
Institution: Roswell Park Comprehensive Cancer Center
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: Acquisition of High Performance Data and Computing Infrastructure to Advance Biomedical Research, Immuno-Oncology Translation Network: Data Management and Resource-Sharing Center at RPCI, G5512794466, Transdisciplinary Research in Energetics and Cancer (TREC) Training Grant, Metformin for chemoprevention of lung cancer in obese subjects at high risk
OpenAlex ID: W4307658068