The immunosuppressive phenotype of tumor-infiltrating neutrophils is associated with obesity in kidney cancer patients
Camilla Margaroli, Maria A. Cardenas, Caroline S. Jansen, Adriana Moon Reyes, Fares Hosseinzadeh, Gordon Hong, Yilin Zhang, Haydn Kissick, Rabindra Tirouvanziam, Viraj A. Master
Abstract
Infiltrating tumor neutrophils and myeloid-derived suppressor cells represent major populations in the tumor microenvironment that contribute to tumor progression. However, the phenotype of circulating and tumor-associated neutrophils, and the impact of cancer patients' metabolic state on neutrophil function need further characterization. Here we show that in kidney cancer patients, circulating neutrophils display an altered immature-like phenotype, and an activated/primed metabolic state. Circulating immature-like neutrophils acquire an activated phenotype upon migration into the tumor tissue, characterized by high expression of the immunosuppressive enzyme arginase-1, and active granule release. Interestingly, obesity and adipose tissue distribution were significantly associated with this activated phenotype of neutrophils, including the release of arginase-1 in the tumor tissue. These results provide a possible functional relationship between the metabolic status of the patients and disease progression, through an active immunosuppressive role of neutrophils within the kidney tumor microenvironment.