Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus Trametinib.
Clin Cancer Res
; 27(16): 4500-4510, 2021 08 15.
Article
in En
| MEDLINE
| ID: mdl-34108180
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 ANDMETHODS:
We 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.RESULTS:
Baseline 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.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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oximes
/
Pyridones
/
Pyrimidinones
/
Skin Neoplasms
/
B-Lymphocytes
/
Antineoplastic Combined Chemotherapy Protocols
/
Imidazoles
/
Melanoma
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Clin Cancer Res
Journal subject:
NEOPLASIAS
Year:
2021
Document type:
Article
Affiliation country:
Suiza