AI Article Synopsis

  • Patients with unresectable or metastatic melanoma often develop resistance to therapies like BRAF and MEK inhibitors, and there's a need for predictive biomarkers to tailor treatments effectively.
  • * A study analyzed tumor samples from 146 patients in a trial and found that a high T-cell/low B-cell gene signature correlated with better overall survival compared to a high T-cell/high B-cell signature.
  • * The results suggest that B cells might serve as a useful biomarker for predicting clinical outcomes in melanoma patients receiving specific targeted therapies, but further research with larger groups is necessary for validation.

Article Abstract

Purpose: Although patients with unresectable or metastatic melanoma can experience long-term survival with BRAF- and MEK-targeted agents or immune checkpoint inhibitors over 5 years, resistance develops in most patients. There is a distinct lack of pretherapeutic biomarkers to identify which patients are likely to benefit from each therapy type. Most research has focused on the predictive role of T cells in antitumor responses as opposed to B cells.

Patients And Methods: We conducted prespecified exploratory biomarker analysis using gene expression profiling and digital pathology in 146 patients with previously untreated V600-mutant metastatic melanoma from the randomized, phase III COMBI-v trial and treated with dabrafenib plus trametinib who had available tumor specimens from screening.

Results: Baseline cell-cycle gene expression signature was associated with progression-free survival ( = 0.007). Patients with high T-cell/low B-cell gene signatures had improved median overall survival (not reached [95% confidence interval (CI), 33.8 months-not reached]) compared with patients with high T-cell/high B-cell signatures (19.1 months; 95% CI, 13.4-38.6 months). Patients with high B-cell signatures had high B-cell infiltration into the tumor compartment, corresponding with decreased MAPK activity and increased expression of immunosuppressive markers.

Conclusions: B cells may serve as a potential biomarker to predict clinical outcome in patients with advanced melanoma treated with dabrafenib plus trametinib. As separate studies have shown an opposite effect for B-cell levels and response to immunotherapy, B cells may serve as a potential biomarker to facilitate treatment selection. Further validation in a larger patient cohort is needed.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401540PMC
http://dx.doi.org/10.1158/1078-0432.CCR-20-3586DOI Listing

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