Centre de Recherche en Cancérologie de Toulouse (CRCT), UMR Inserm-CNRS-Toulouse University
host: Laurent GROS (IRCM)
The combination of anti-PD-1 and anti-CTLA-4 boosts the anti-cancer immune response in patients with advanced melanoma. However, 60% of patients fail to respond or relapse early after induction, and 95% develop immune-related adverse events (irAEs) such as colitis, which can be treated with infliximab, a tumour necrosis factor-alpha inhibitor (TNFi). The impact of TNFi on immune and clinical responses remains to be elucidated. Here we provide evidence that TNF blockade can improve the response to the anti-PD-1 and anti-CTLA-4 combination not only in mice but also in patients enrolled in a phase 1b clinical trial (TICIMEL, NTC03293784). However, certolizumab, but not infliximab, strongly stimulates immune and therapeutic responses to ICI. Mechanistically, we have shown that the IgG1 Fc fragment of infliximab impairs the ability of TNF blockade to stimulate the efficacy of ICI therapy.
Situé dans le Parc Euromédecine, l'Institut de Recherche en Cancérologie de Montpellier (U1194) est localisé sur le Campus Val d'Aurelle (ICM, Institut régional du Cancer Montpellier / Val d'Aurelle).
Centre de Recherche U1194 soutenu par l'Inserm, l'Université de Montpellier et l'Institut du Cancer de Montpellier (ICM)
Institut de Recherche en Cancérologie de
