intratumoral injection of ifnalpha dendritic cells after dacarbazine activates antitumor immunity results from a phase i trial in advanced melanoma background advanced melanoma patients have an extremely poor long term prognosis and are in strong need of new therapies the recently developed targeted therapies have resulted in a marked antitumor effect but most responses are partial and some degree of toxicity remain the major concerns dendritic cells play a key role in the activation of the immune system and have been typically used as ex vivo antigenloaded cell drugs for cancer immunotherapy another approach consists in intratumoral injection of unloaded dcs that can exploit the uptake of a wider array of tumorspecific and individual unique antigens however intratumoral immunization requires dcs endowed at the same time with properties typically belonging to both immature and mature dcs ie antigen uptake and t cell priming dcs generated in presence of interferonalpha ifndcs due to their features of partially mature dcs capable of efficiently uptaking processing and crosspresenting antigens to t cells could successfully carry out this task combining intratumoral immunization with tumordestructing therapies can induce antigen release in situ facilitating the injected dcs in triggering an antitumor immune responsemethods we tested in a phase i clinical study in advanced melanoma a chemoimmunotherapy approach based on unloaded ifndcs injected intratumorally one day after administration of dacarbazine primary endpoint of the study was treatment safety and tolerability secondary endpoints were immune and clinical responses of patientsresults six patients were enrolled and only three completed the treatment the chemoimmunotherapy was well tolerated with no major side effects three patients showed temporary disease stabilization and two of them showed induction of t cells specific for tyrosinase nyeso1 and gp100 of interest one patient showing a remarkable longterm disease stabilization kept showing presence of tyrosinase specific t cells in pbmc and high infiltration of memory t cells in the tumor lesion at 21 monthsconclusion we tested a chemoimmunotherapeutic approach based on ifndcs injected intratumorally one day after dtic in advanced melanoma the treatment was well tolerated and clinical and immunological responses including development of vitiligo were observed therefore warranting additional clinical studies aimed at evaluating efficacy of this approachtrial registration trial registration number not publicly available due to eudract regulations