e-Article
Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus TrametinibTumor B-Cell Role in Outcome With Dabrafenib + Trametinib
Document Type
article
Author
Brase, Jan C; Walter, Robert FH; Savchenko, Alexander; Gusenleitner, Daniel; Garrett, James; Schimming, Tobias; Varaljai, Renata; Castelletti, Deborah; Kim, Ju; Dakappagari, Naveen; Schultz, Ken; Robert, Caroline; Long, Georgina V; Nathan, Paul D; Ribas, Antoni; Flaherty, Keith T; Karaszewska, Boguslawa; Schachter, Jacob; Sucker, Antje; Schmid, Kurt W; Zimmer, Lisa; Livingstone, Elisabeth; Gasal, Eduard; Schadendorf, Dirk; Roesch, Alexander
Source
Clinical Cancer Research. 27(16)
Subject
Language
Abstract
PurposeAlthough 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 methodsWe conducted prespecified exploratory biomarker analysis using gene expression profiling and digital pathology in 146 patients with previously untreated BRAF 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.ResultsBaseline cell-cycle gene expression signature was associated with progression-free survival (P = 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.ConclusionsB 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.