Took a L, but tonight I bounce back.

Immunotherapy and BRAF/MEK targeted therapy have proven success, first in metastatic melanoma and then in resected node positive melanoma. But they’re not a silver bullet. You may remember that melanomas treated withBRAF/MEK inhibition become “addicted” to the inhibition of this pathway via ERK2 kinase. In a related fashion, the current study describes an “ectopic” expression of PD-1 by a subset of melanoma cells as a means of evading targeted kill. Tumors usually express PD-L1 (the ligand) while immune cells express PD-1 (the receptor). Remarkably, BRAF/MEK inhibition enriched a population of melanoma cells expressing PD-1 (the receptor). These cells exhibited “stemness” features, suggesting PD-1 expression may be an unexpected means of resisting therapy. More remarkably, the addition of anti-PD1 to BRAF/MEK inhibition in immune deficient mice demonstrated prolonged tumor response. TBL: Anti-PD1 inhibition may directly target melanoma stem cells tired of taking a L in the setting of BRAF/MEK inhibition. | Sanlorenzo, Clin Cancer Res 2018