Distinct Functions of Senescence-Associated Immune Responses in Liver Tumor Surveillance and Tumor Progression
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels des chimiokines secrétées par des hépatocytes en sénescence sont susceptibles de prévenir le développement d'une tumeur hépatique mais également d'accélérer la progression d'un carcinome hépatocellulaire lorsqu'il est complètement formé
Oncogene-induced senescence causes hepatocytes to secrete cytokines, which induce their immune-mediated clearance to prevent tumor initiation, a process termed ?senescence surveillance.? However, senescent hepatocytes give rise to hepatocellular carcinomas (HCCs), if the senescence program is bypassed or if senescent cells are not cleared. Here, we show context-specific roles for CCR2+ myeloid cells in liver cancer. Senescence surveillance requires the recruitment and maturation of CCR2+ myeloid cells, and CCR2 ablation caused outgrowth of HCC. In contrast, HCC cells block the maturation of recruited myeloid precursors, which, through NK cell inhibition, promote growth of murine HCC and worsen the prognosis and survival of human HCC patients. Thus, while senescent hepatocyte-secreted chemokines suppress liver cancer initiation, they may accelerate the growth of fully established HCC.