English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background   MAP2K1/2  genes are mutated in approximately 8% of melanoma patients; however, the impact of  MAP2K1/2  gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between  MAP2K1/2  gene mutations and the treatment response.    Methods  Six metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation.    Results  Compared to patients with wild-type  MAP2K1/2 , those with  MAP2K1/2  mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between  MAP2K1/2  mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with  MAP2K1/2  mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with  MAP2K  mutation was enriched in CD8 +  T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with  MAP2K1/2  mutations from anti-CTLA-4 treatment.    Conclusions   MAP2K1/2  mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with  MAP2K1/2- mutated melanoma.

The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma