Page 33 - Hormel Report 2023

ORCID iD: https://orcid.org/0000-0002-7052-6513
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(A) Social isolation (SI) increases the growth
of E0771 mammary tumors in C57BL/6 mice. (B) E0771 mammary tumors grow bigger
in group-housed (GH) mice which received fecal microbiota by oral gavage from SI mice, compared with receiving fecal microbiota from GH mice. (C) Antibiotic treatment that reduces all bacteria in the gut prevents the increase in E0771 tumor growth in SI mice. (D) Short-chain
fatty acid receptor FFAR2 levels are reduced in anti-tumor CD8+ T cells and myeloid cells which present antigens to activate CD8+ T cells.
(A) Maternal obesity leads to gut dysbiosis in the offspring, mani- fested as higher levels of Prevotella sp and reduced abundance of bac- teria producing short-chain fatty acids (SCFAs). (B) High abundance of Prevotella sp and reduced levels of SCFAs affect the tumor immune responses, prompting ineffective immunotherapy response. Due
to the reduced number of CD8+ T
cells, anti-PD1 treatment cannot
activate sufficient numbers of
CD8+ T cells and consequently
does not inhibit tumor growth.
Further, maternal obesity also
increases the frequency of
immunosuppressive cells, such
as myeloid-derived suppressor
cells (MDSC) in the tumor microen-
vironment (TME) (C) Dietary interventions that increase the abundance of bacteria producing SCFAs and decrease Prevotella, such as supplementation with dietary fiber, potentially reverses offspring’s resistance to breast cancer immunotherapy through increasing CD8+ T cells (D) In this condition, anti-PD1 treatment will induce tumor immune response preventing CD8+ T cells exhaustion (F) Creat- ed with BioRender.com. Published in Cancer Rep (Hoboken). 2022 Dec;5(12):e1752.
“About 50,000 new cases of cancer in the US, especially breast cancer, are attributed to obesity. Socially isolated breast cancer survivors have a 43% higher risk of recurrence and a 64% higher risk of breast cancer-specific mortality than socially integrated survivors.”
Leena Hilakivi-Clarke
PUBLICATION HIGHTLIGHTS:
• Andrade, F. D. O., Jin, L., Clarke, R., Wood, I., Dutton, M., Anjorin, C., Rubin, G., Gao, A., Sengupta, S., FitzGerald, K., & Hilakivi-Clarke, L. (2023). Social Isolation Activates Dormant Mammary Tumors, and Modifies Inflammatory and Mitochondrial Metabolic Pathways in the Rat Mammary Gland. Cells, 12(6), 961.
• Andrade, F. D., Verma, V., & Hilakivi-Clarke, L. (2022). Maternal obesity and resistance to breast cancer treatments among offspring: Link to gut dysbiosis. Cancer Reports, 5(12), 16.
• Hilakivi-Clarke, L., Verma, V., McDermott, M., Koak, P., & Andrade, F. d. O. (2022). Foods may modify responsiveness to cancer immune checkpoint blockers by altering both the gut microbiota and activation of estrogen receptors in immune cells. Frontiers in Microbiomes, 1, 1049688.