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.

doi:10.1101/2022.04.16.488543

bioRxiv · 10.1101/2022.04.16.488543

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.

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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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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.. 2022-04-16. Bone marrow haematopoietic stem cells influence liver homeostatic networks and cancer development after dietary intervention. https://doi.org/10.1101/2022.04.16.488543

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