%0 Journal Article %T Safety of sitagliptin in treatment of hepatocellular carcinoma in chronic liver disease patients %+ Université Paris Cité (UPCité) %+ Immunobiologie des Cellules dendritiques %+ Service d'hépatologie médicale [CHU Cochin] %+ CHU Pitié-Salpêtrière [AP-HP] %A Hollande, Clémence %A Boussier, Jeremy %A Mottez, Estelle %A Bondet, Vincent %A Buivan, Tan, Phuc %A Charbit, Bruno %A Llibre, Alba %A Charlotte, Frédéric %A Savier, Eric %A Scatton, Olivier %A Duffy, Darragh %A Albert, Matthew %A Mallet, Vincent %A Pol, Stanislas %Z Fondation ARC pour la Recherche sur le Cancer %< avec comité de lecture %@ 2642-3561 %J Liver Cancer International %P Online Version of Record before inclusion in an issue %8 2021-08-28 %D 2021 %R 10.1002/lci2.36 %K dipeptidyl peptidase 4 %K hepatocellular carcinoma %K leucocyte trafficking %K neoadjuvant therapy %K sitagliptin %Z Life Sciences [q-bio]Journal articles %X Background & Aims : Systemic therapies for hepatocellular carcinoma (HCC) treatment have limited efficacy and poor safety. Dipeptidyl peptidase-4 inhibitors were initially developed and approved as treatment for type 2 diabetes, yet oral administration of sitagliptin has recently been shown to improve naturally occurring tumour immunity in animal models of HCC.Methods : We conducted a phase Ib clinical trial to evaluate the impact of a pre-operative 3-week DPP4 inhibitor (sitagliptin) treatment in HCC patients undergoing liver resection. The primary objective was to evaluate the safety of a sitagliptin treatment in each of the three groups of patients, according to an escalating dosage of sitagliptin (100, 200 and 600 mg/d). Secondary objectives included the assessment of DPP4 activity, cytokine expression in plasma samples and circulating immune populations.Results : Fourteen patients were included and analysed. In all three dose groups, no severe adverse event related to sitagliptin was reported. A significant inhibition of DPP4 activity was observed upon sitagliptin treatment, which prevented the N-terminal truncation of CXCL10, leading to a mobilization of circulating CD8+ T cells and eosinophils. Immunochemistry analysis showed a lymphoid infiltration in all tumour samples with the presence of a population of CXCR3+ T cells in all but one of the tumours. Positivity for CXCL10 (IP10) and CCR3 in tumour and/or stroma cells was found in all resection pieces.Conclusion : In summary, sitagliptin can be used safely in patients with chronic liver disease and HCC, and could be tested in phase 2 trial, as an adjuvant in combination with others drugs, for the treatment of HCC patients. %G English %2 https://pasteur.hal.science/pasteur-03384283/document %2 https://pasteur.hal.science/pasteur-03384283/file/Safety_of_sitagliptin_in_treatment_of_hepatocellul.pdf %L pasteur-03384283 %U https://pasteur.hal.science/pasteur-03384283 %~ INSERM %~ PASTEUR %~ APHP %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ SU-MEDECINE %~ SU-MED %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ SU-TI %~ ALLIANCE-SU