ABSTRACT
Lifestyle factors exert profound effects on host physiology and immunology. Disparities in cancer outcomes persist as a complex and multifaceted challenge, necessitating a comprehensive understanding of the interplay between host environment and antitumor immune responses. Determinants of health - such as obesity, diet, exercise, stress, or sleep disruption - have the potential for modification, yet some exert long-lasting effects and may challenge the notion of complete reversibility. Herein we review intersectional considerations of lifestyle immunity and the impact on tumor immunology and disparities in cancer outcomes, with a focus on obesity.
Subject(s)
Neoplasms , Humans , Neoplasms/epidemiology , Obesity/epidemiology , Diet , Life Style , ExerciseABSTRACT
Obesity is characterized by chronic systemic inflammation and enhances cancer metastasis and mortality. Obesity promotes breast cancer metastasis to lung in a neutrophil-dependent manner; however, the upstream regulatory mechanisms of this process remain unknown. Here, we show that obesity-induced monocytes underlie neutrophil activation and breast cancer lung metastasis. Using mass cytometry, obesity favors the expansion of myeloid lineages while restricting lymphoid cells within the peripheral blood. RNA sequencing and flow cytometry revealed that obesity-associated monocytes resemble professional antigen-presenting cells due to a shift in their development and exhibit enhanced MHCII expression and CXCL2 production. Monocyte induction of the CXCL2-CXCR2 axis underlies neutrophil activation and release of neutrophil extracellular traps to promote metastasis, and enhancement of this signaling axis is observed in lung metastases from obese cancer patients. Our findings provide mechanistic insight into the relationship between obesity and cancer by broadening our understanding of the interactive role that myeloid cells play in this process.
