Pieper, et al. – Summary
Pieper N, Zaremba A, Leonardelli S, Harbers FN, Schwamborn M, Lübcke S, Schrörs B, Baingo J, Schramm A, Haferkamp S, Seifert U, Sucker A, Lennerz V, Wölfel T, Schadendorf D, Schilling B, Paschen A, Zhao F. Evolution of melanoma cross-resistance to CD8+ T cells and MAPK inhibition in the course of BRAFi treatment. Oncoimmunology. 2018 Apr 18;7(8):e1450127. Available at: https://www.tandfonline.com/doi/full/10.1080/2162402X.2018.1450127
Approximately 50% of melanomas show activating BRAFV600 mutations mediating tumor cell proliferation by constitutive BRAF-MEK-ERK (MAPK) pathway signaling. BRAF and MEK inhibitors can block MAPK pathway activation and their application leads to profound but frequently transient clinical responses. In order to improve patient outcomes combinations of targeted MAPK inhibitor (MAPKi) therapy and immunotherapy are currently tested in clinical trials. Immunotherapy exploits the capacity of T cells to kill tumor cells. This work shows that prolonged exposure of melanoma cells to MAPKi impairs their recognition by T cells, suggesting a risk of cross-resistance development of melanoma to targeted therapy and immunotherapy under combined treatment.
Led by researchers in Essen, with involvement of the MELGEN student Sonia Leonardelli and colleagues from different research groups in Germany.