Bone marrow haematopoietic stem cells influence liver homeostatic networks and cancer development after dietary intervention
Alipour Talash, G.; Langfelder, P.; Vitale, D.; Karimi Azardaryany, M.; Belgard, T. G.; Choo, J.; Rogers, G.; Ho, V.; Ramezani-Moghadam, M.; Dervish, S.; Lai, J.; Gloss, B. S.; McLeod, D.; Eslam, M.; Liddle, C.; Qiao, L.; George, J.; Esmaili, S.
Show abstract
A holistic understanding of anti-tumor immunity requires examination of systemic immunity beyond the tumor microenvironment. This link between systemic and tumor immune activity is underexplored. We demonstrate that a stronger Type I interferon response in human liver tumors predicts better survival and correlates with the immune response in the adjacent non-tumor liver. Further, in patients with liver cancer, clonal hematopoiesis (CH) (a marker of systemic immune activation) is associated with a trend towards improved survival. In a mouse model of liver cancer, basal liver immune responses correlate with the degree of bone marrow hematopoietic stem and progenitor cell responses. A higher systemic and liver immune response, marked by innate myeloid cell infiltration reduces tumor burden, while sub-optimal systemic and liver immunity corresponded with a higher tumor burden. Our findings indicate that the state of bone marrow hematopoiesis impacts liver tumor outcomes, offering both therapeutic and prognostic opportunities.
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