Discussion
NKT cell dysfunction, cancer, death, melanoma
RECURRENCE, MELANOMA, PROLIFERATION, CANCER, STAGE III MELANOMA
In this randomised study, fully resected high-risk melanoma patients were assigned to receive autologous DC-based vaccines loaded with long peptides from NY-ESO-1 alone, or the peptides loaded together with the NKT cell agonist The vaccine-induced T cell responses observed could be detected in PBMCs evaluated directly ex vivo by IFN-γ ELISpot, using the long NY-ESO-1-derived peptides as recall agents. There are only a few other reports where NY-ESO-1-specific T cell responses have been detected so readily without requiring several days of in vitro restimulation with antigen [The lack of significant effect of including A likely explanation for the lack of T cell enhancement with It is possible that NKT cell function was impaired in the patient cohort. There have been previous reports of NKT cell dysfunction in cancer patients [It should be noted that the modest levels of NKT cell proliferation observed in this trial are in contrast to a comparable study conducted by Chang et al., with Given that effective NKT cell helper function in animals is typically associated with extensive NKT cell proliferation, the weak proliferation observed in vivo here was perhaps insufficient to meet the threshold required for adjuvant activity. The dose of The NY-ESO-1 antigen used in this study has been targeted by vaccines in several previous clinical studies. In a retrospective analysis of early phase clinical trials of adjuvant NY-ESO-1-based vaccine immunotherapy (using DCs, peptide in adjuvant, or peptides with toll-like receptor agonists), Lattanzi et al. compared 67 vaccinated patients with resected stage III melanoma to 123 historical control patients who received no adjuvant therapy and found that the vaccine was associated with decreased risk of recurrence and death [Overall, this study failed to demonstrate a significant advantage to loading peptide-pulsed MoDCs with