Background The role of T regulatory lymphocytes (Tregs) and their immunosuppressive mechanisms in the context of programmed death (PD)-1 blockade is not completely understood. Objectives To assess the impact of PD-1-blocking antibody treatment on Treg subpopulations in the blood. Methods We studied circulating Treg subpopulations in patients with melanoma under nivolumab or pembrolizumab treatment using flow cytometry and correlated these findings with clinical outcomes. Results These analyses revealed that the frequency of CD4 + CD25 ++ CD127 À PD-1 + lymphocytes (PD-1 + Tregs) significantly decreased after the first cycle of immunotherapy (23% vs. 8Á6%, P = 0Á043). Compared with patients who did not show a significant decline of PD-1 + Tregs after the first treatment, those who did had better clinical outcomes with respect to progression-free survival (PFS, P = 0Á022) and melanoma-specific death (MSD, P = 0Á0038). Multivariate analysis confirmed that a significant decline of PD-1 + Tregs in peripheral blood after the first treatment cycle is a significant predictor of more favourable PFS and MSD (P = 0Á04 and 0Á017, respectively). Interestingly, the occurrence of immune-related adverse events was also an independent predictor for decreased risk of MSD (P = 0Á047; odds ratio 0Á064, 95% confidence interval 0Á0042-0Á97). Conclusions We provide preliminary evidence that circulating PD-1 + Tregs rapidly decline after the initiation of treatment with PD-1-blocking antibodies, which is associated with reduced risk of melanoma progression and MSD. Patients showing no decrease of these PD-1 + Tregs in peripheral blood are characterized by an impaired response to immune checkpoint blockade and worse outcome.What's already known about this topic?• Programmed death (PD)-1-blocking antibodies are highly effective in melanoma treatment.• However, more than half of patients do not benefit from this therapy and to date it is difficult to predict which patients will respond to it.What does this study add?• PD-1-blocking antibody therapy rapidly results in a decline of circulating PD-1 + T regulatory cells (Tregs).
Introduction: Few studies have evaluated patient-reported outcome measures and the effect of patient educational materials in German patients with skin cancer. We conducted a prospective study to measure the impact of treatment on health-related quality of life in German patients with skin cancer, identify variables that may contribute to changes in health-related quality of life, and evaluate the effect of providing additional information through a patient education brochure.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.