Details

Autor(en) / Beteiligte

• Brase, Jan C
• Walter, Robert F H
• 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

Titel

Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus Trametinib

Ist Teil von

• Clinical cancer research, 2021-08, Vol.27 (16), p.4500-4510

Ort / Verlag

United States: American Association for Cancer Research

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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.