Imatinib in Dermatofibrosarcoma: Targeted Therapy or Immunotherapy? Selma Ugurel, Jürgen C. Becker  Journal of Investigative Dermatology  Volume 137, Issue 2, Pages 277-279 (February 2017) DOI: 10.1016/j.jid.2016.10.027 Copyright © 2016 The Authors Terms and Conditions

Figure 1 PDGFR blockade and immune modulation by imatinib in FS-DFSP. (a) Fusion of the genes encoding PDGFB and COL1A1 in DFSP cells results in a constitutively activated PDGFR signaling pathway by autocrine stimulation. The tumor cells exhibit enhanced proliferation, reduced cell surface expression of HLA class I and PD-L1, and impaired antigen presentation. As a result, there are low numbers of tumor-infiltrating T cells. (b) After treatment with imatinib, autocrine stimulation of the PDGFR pathway is inhibited. The tumor characteristics change into high proinflammatory cytokines and chemokines in the microenvironment, enhanced cell cycle inhibition and induction of apoptosis, and increased cell surface expression of HLA class I cell surface molecules. Consequently, enhanced antigen presentation results in a dense infiltration of the tumor by T cells and strong PD-L1 expression on the tumor cells themselves. DFSP, dermatofibrosarcoma; FS-DFSP, dermatofibrosarcoma with sarcomatous transformation; PDGF, platelet-derived growth factor; PDGF-R, platelet-derived growth factor receptor. Journal of Investigative Dermatology 2017 137, 277-279DOI: (10.1016/j.jid.2016.10.027) Copyright © 2016 The Authors Terms and Conditions