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BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma

Clinical Cancer Research · 2013 · Vol. 19(5) · pp. 1225–1231

Dennie T. Frederick(Brigham and Women's Hospital)Adriano Piris(Brigham and Women's Hospital)Alexandria P. Cogdill(Brigham and Women's Hospital)Zachary A. Cooper(Brigham and Women's Hospital)Cecilia Lezcano(Brigham and Women's Hospital)Cristina R. Ferrone(Brigham and Women's Hospital)Devarati Mitra(Brigham and Women's Hospital)Andrea Boni(Brigham and Women's Hospital)Lindsay P. Newton(Brigham and Women's Hospital)Chengwen Liu(Brigham and Women's Hospital)Weiyi Peng(Brigham and Women's Hospital)Ryan J. Sullivan(Brigham and Women's Hospital)Donald P. Lawrence(Brigham and Women's Hospital)F. Stephen Hodi(Brigham and Women's Hospital)Willem W. Overwijk(Brigham and Women's Hospital)Gregory Lizée(Brigham and Women's Hospital)Gëorge F. Murphy(Brigham and Women's Hospital)Patrick Hwu(Brigham and Women's Hospital)Keith T. Flaherty(Brigham and Women's Hospital)David E. Fisher(Brigham and Women's Hospital)Jennifer A. Wargo✉(Brigham and Women's Hospital)

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Abstract

Together, these data suggest that treatment with BRAF inhibition enhances melanoma antigen expression and facilitates T-cell cytotoxicity and a more favorable tumor microenvironment, providing support for potential synergy of BRAF-targeted therapy and immunotherapy. Interestingly, markers of T-cell exhaustion and the immunosuppressive ligand PDL1 are also increased with BRAF inhibition, further implying that immune checkpoint blockade may be critical in augmenting responses to BRAF-targeted therapy in patients with melanoma.

Melanoma and MAPK Pathways Cytokine Signaling Pathways and Interactions Computational Drug Discovery MethodsMelanomaTumor microenvironmentMetastatic melanomaCancer researchMedicineAntigenCancerImmunologyTumor cellsInternal medicine

MeSH terms

VemurafenibFluorescent Antibody TechniqueHumansImidazolesIndolesMelanomaNeoplasm StagingOximesPrognosisPyridonesPyrimidinonesRNA, MessengerSulfonamidesBiomarkers, TumorBlotting, Western