ESPEN 2020 Abstract Submission

Topic: Nutrition and cancer

Abstract Submission Identifier: ESPEN20-ABS-1542

SPONTANEOUS PHYSICAL ACTIVITY IN OBESE CONDITIONS MODULATES TISSUE HORMONAL SIGNALS LEADING TO REDUCED MAMMARY TUMOUR GROWTH

D. Le Guennec^*, ¹, M. Goepp ¹, S. Rougé ¹, M.-C. Farges ¹, J. Talvas ¹, N. Goncalves-Mendes ¹, F. Caldefie-Chezet ², M.-P. Vasson ¹, A. Rossary ¹

¹Laboratoire de biochimie, biologie moléculaire et nutrition ; Equipe ECREIN ; UMR1019 UNH, ²Laboratoire de sciences végétales et fongiques pharmaceutiques, Equipe ECREIN, UMR 1019 INRAE UCA, UNIVERSITÉ CLERMONT AUVERGNE - INRA, Clermont-Ferrand, France

Rationale: In obesity, deregulation of adipose tissue induce chronic inflammation that promotes a pro-carcinogenic microenvironment and breast cancer development. In addition, aging is associated with a decline in immune function called immunosenescence, affecting both the function and phenotype of innate and adaptive immune cells. The aging immune system is characterized by a pro-inflammatory environment with the secretion of cytokines such as IL-1, TNF-α and IL-6. Conversely, physical activity is a factor in the prevention of obesity, immunosenescence and cancers through an increased anti-inflammatory response and stimulation of the immune system. However, the protective mechanisms of spontaneous physical activity (PA) in obese situations on breast carcinogenesis are poorly understood. The aim of this study is to characterize the impact of spontaneous PA on tumour growth in a murine breast carcinogenesis model associated with obesity.

Methods: Elderly C57BL/6 mice (33 weeks old, n=10/group), ovariectomised, fed with a high fat diet, are housed in standard (SE) or enriched (EE) environments. After 6 weeks, EO771 syngeneic tumour cells are implanted by fat-pad in the fourth right mammary gland before sacrificing. A marker analysis of inflammation, metabolism and cytokine secretions was performed on tumour, gastrocnemius, inguinal adipose tissue and mouse plasma. An analysis of tumour immune recruitment was conducted.

Results: The enriched environment induces an increase in the level of physical activity per day, with a decrease recognized circulating markers of physical activity such as myostatin and IL-6. Tumour growth is slowed in EE mice compared to ES mice (EE =634 ± 388 mm³, ES=1572 ± 678 mm³, p<0.05) with an increase in survival. Within tumours, EE induces a decrease in the quantity of lymphoid cells with a decrease in Th2 (0.9%), Treg (20.1%) and MDCS (13.6%); and conversely a greater quantity of Tc (14.6%) and TAMs (22.6%). While no change in tumour NKs is observed, granzyme B is increased as well as the expression of perforin 1 and granzyme A. In the gastrocnemius, the amount of leptin is strongly decreased, positively correlating with the amount of intra-tumour leptin. In the inguinal fat tissue, leptin and adiponectin levels are unchanged despite an increase in circulating adiponectin.

Conclusion: These results show that spontaneous physical activity in obese conditions slows tumour growth by reducing low-grade inflammation, modulating the recruitment and effectiveness of the immune system within the tumour.

Disclosure of Interest: None Declared

Keywords: breast cancer, Physical activity