With the present study, the first evidence is provided that the increase of CD4+CD25 high T cells and FoxP3 transcripts is associated with operational tolerance in liver transplanted patients during IS withdrawal.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared the transcriptional profile of PDGFRα CAFs isolated from genetically engineered mouse PDAC tumors with that of normal pancreatic fibroblasts to identify genes potentially implicated in their protumorigenic properties. We report that the most differentially expressed gene, , a member of the serum amyloid A (SAA) apolipoprotein family, is a key mediator of the protumorigenic activity of PDGFRα CAFs. Whereas -competent CAFs stimulate the growth of tumor cells in an orthotopic model,-null CAFs inhibit tumor growth. Saa3 also plays a role in the cross talk between CAFs and tumor cells. Ablation of in pancreatic tumor cells makes them insensitive to the inhibitory effect of-null CAFs. As a consequence, germline ablation of does not prevent PDAC development in mice. The protumorigenic activity of Saa3 in CAFs is mediated by Mpp6, a member of the palmitoylated membrane protein subfamily of the peripheral membrane-associated guanylate kinases (MAGUK). Finally, we interrogated whether these observations could be translated to a human scenario. Indeed,, the ortholog of murine Saa3, is overexpressed in human CAFs. Moreover, high levels of in the stromal component correlate with worse survival. These findings support the concept that selective inhibition of SAA1 in CAFs may provide potential therapeutic benefit to PDAC patients.

The vena cava preservation technique can be used routinely in orthotopic liver transplantation because it is safe and efficient and involves few surgical complications especially if for venous reconstruction we use the patch obtained by joining the three suprahepatic veins.

Highlights d Combined Egfr/Raf1 ablation results in complete regression of a subset of PDACs d Mouse mutant Kras/Trp53-induced PDACs display distinct transcriptional profiles d PDAC transcriptional profiles determine their response to Egfr/Raf1 ablation d EGFR/c-RAF inhibition also prevents proliferation of PDXderived tumor cells