American Association for Cancer Research
cd-22-1062_supplementary_figure_s4_suppsf4.pdf (668.81 kB)

Supplementary Figure S4 from Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis

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journal contribution
posted on 2023-06-26, 13:00 authored by Omer Goldman, Lital N. Adler, Emma Hajaj, Tommaso Croese, Naama Darzi, Sivan Galai, Hila Tishler, Yarden Ariav, Dor Lavie, Liat Fellus-Alyagor, Roni Oren, Yuri Kuznetsov, Eyal David, Rami Jaschek, Chani Stossel, Oded Singer, Sergey Malitsky, Renana Barak, Rony Seger, Neta Erez, Ido Amit, Amos Tanay, Ann Saada, Talia Golan, Tamar Rubinek, Joo Sang Lee, Shay Ben-Shachar, Ido Wolf, Ayelet Erez

Supplementary Figure S4 demonstrates similar transcriptional and metabolic changes following liver infiltration of immune cells to the liver of PDAC mice



Multiple studies have identified metabolic changes within the tumor and its microenvironment during carcinogenesis. Yet, the mechanisms by which tumors affect the host metabolism are unclear. We find that systemic inflammation induced by cancer leads to liver infiltration of myeloid cells at early extrahepatic carcinogenesis. The infiltrating immune cells via IL6–pSTAT3 immune–hepatocyte cross-talk cause the depletion of a master metabolic regulator, HNF4α, consequently leading to systemic metabolic changes that promote breast and pancreatic cancer proliferation and a worse outcome. Preserving HNF4α levels maintains liver metabolism and restricts carcinogenesis. Standard liver biochemical tests can identify early metabolic changes and predict patients’ outcomes and weight loss. Thus, the tumor induces early metabolic changes in its macroenvironment with diagnostic and potentially therapeutic implications for the host. Cancer growth requires a permanent nutrient supply starting from early disease stages. We find that the tumor extends its effect to the host's liver to obtain nutrients and rewires the systemic and tissue-specific metabolism early during carcinogenesis. Preserving liver metabolism restricts tumor growth and improves cancer outcomes.

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