Immune markers in the RASopathy neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a genetic disorder with an early mortality determined mostly by malignancy. Little is known about the immunosurveillance factors in NF1 patients. In this study we evaluated inflammatory markers and their cellular sources in NF1 patients to try understanding the relation of immune factors and the tumorigenesis that characterizes the disease. Using flow cytometry and ELISA, we assayed cytokines, co-stimulatory molecules, the functional state of circulating blood cells and cytokine plasma levels in a case-control transversal study. The frequency of CD4+ T cells seems reduced. In addition, a shift towards an anti-inflammatory profile was observed in cells expressing cytokines, except for a small subpopulation of CD8+ T cells that displayed an increased frequency of cells expressing the pro-inflammatory cytokine Tumor necrosis factor (TNF-α), while plasma soluble levels of Transforming growth factor-beta (TGF-β) and interleukin-6 (IL-6) were increased in NF1 patients. Knowledge of the regulation of NF1 and the role of TGF-beta signaling pathway in malignant peripheral nerve sheath tumor pathogenesis might shed light on molecular carcinogenesis mechanisms and lead to putative interventions both in prevention and treatment of malignant tumors.