Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus Trametinib
Year: 2021
Type: 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: 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: = 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.
Source: Clinical Cancer Research
Authors: Jan C. Brase, Robert F.H. Walter, Alexander Savchenko, Daniel Gusenleitner, James Garrett, Tobias Schimming, Renata Varaljai, Deborah Castelletti, Ju Kim, Naveen Dakappagari, Ken Schultz, Caroline Robert, Georgina V. Long, Paul D. Nathan, Antoni Ribas, Keith T. Flaherty, Boguslawa Karaszewska, Jacob Schachter, Antje Sucker, Kurt W. Schmid, Lisa Zimmer, Elisabeth Livingstone, Eduard Gasal, Dirk Schadendorf, Alexander Roesch
Institutions: Novartis (Switzerland), Ruhrlandklinik, Essen University Hospital, University of Duisburg-Essen, Fachklinik Hornheide, Navigate BioPharma (United States), The University of Sydney, Melanoma Institute Australia, Mount Vernon Cancer Centre, University of California, Los Angeles, Harvard University, Massachusetts General Hospital, Tel Aviv University, Sheba Medical Center, Deutsches Konsortium für Translationale Krebsforschung
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funder: Deutsche Forschungsgemeinschaft
Awards: G3874085344, G6470104738
OpenAlex ID: W3166541179