AuthOr’s VIew AuthOr’s VIew

T cell-based immunotherapies have the potential to induce long-lasting complete remissions in cancer patients. However, their efficacy is often limited by immuno-suppressive cells and factors found within the tumor microenvironment, which pro-tect the tumor from immune recognition and killing by cytotoxic T lymphocytes (CTLs).1 While several tumor-specific mechanisms of immunosuppression have been described, how immunosuppression is initiated and sustained within neoplastic lesions to promote tumor growth remains to be elucidated. We have recently shown that immunosuppression can be initiated by oncogenic BRAF, which is mutated to a constitutively active form, BRAFV600E, in> 50 % of melanoma patients.2 This pathway of immunosuppression involves a molecular cross-talk between BRAFV600E-expressing tumor cells and tumor-asso-ciated fibroblasts (TAF) and features the upregulation of a transcriptional program involving multiple immunomodulatory genes known to inhibit immune responses (Fig. 1). Collectively, our results suggest that cancer-associated chronic immuno-suppression may be relieved through the pharmacological inhibition of the MAPK signaling pathway in tumor cells, and predict that such an intervention would strongly synergize with immunotherapy. Although the BRAFV600E-mediated activation of the MAPK signaling pathway Forging a link between oncogenic signaling and immunosuppression in melanoma Jahan s. Khalili, Patrick hwu and Gregory Lizée