Highlights of This Issue

Abstract

Currently sentinel lymph node biopsy is the strongest prognosticator for cutaneous melanoma; however, two of every three patients who die from melanoma have a negative sentinel lymph node biopsy result, reflecting limitations of the procedure and the clinical significance of nonlymphatic spread of disease. Gerami and colleagues report the first of two clinical validation studies of a 31 gene expression profile test that accurately identifies over 85% of patients who eventually develop distant metastasis from cutaneous melanoma. In the current era of melanoma therapy advances, these patients can now be clinically upstaged for appropriate monitoring and early disease progression intervention.Strategies to overcome the immunosuppressive effects of myeloid derived suppressor cells (MDSCs) require downregulation of nitric oxide and arginase-1. Phosphodiesterase-5 (PDE5) inhibitors can effectively reverse MDSC-mediated immune dysfunction in murine models. Califano and colleagues describe the first clinical trials demonstrating the ability of the PDE5 inhibitor, tadalafil, in head and neck cancer to inhibit MDSC-mediated immune suppression and augment T-cell function. These findings establish the rationale for integrating this approach in immune-based anticancer therapies.PDE5 inhibition was shown to downregulate myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) in preclinical models. To evaluate if the same findings hold true in humans, Weed and colleagues performed a phase II clinical trial in which HNSCC patients received the PDE5 specific inhibitor Tadalafil preoperatively. The authors showed that chronic PDE5 inhibition effectively reduces MDSCs from the blood and the tumor of treated patients and increase tumor specific immunity. This finding indicates a safe and effective therapeutic strategy to revert tumor induced immunosuppression in HNSCC, opening the road for a possible combinatorial immunological-based treatment of this malignancy.The genomic landscape of choroid plexus tumors has not been fully elucidated due to limited tumor availability. Investigating the largest cohort of choroid plexus tumors to date, Merino and colleagues have identified unique genomic alterations that define novel molecular subgroups. Although considered pathologically different, choroid plexus papillomas and atypical choroid plexus papillomas exhibit similar molecular profiles and favorable survival. Choroid plexus carcinomas exhibit distinct molecular subgroups, and patients with an elevated number of mutant p53 copies have significantly reduced survival. The integrative genomic approach conducted was ideal to uncover alterations that will guide the clinical stratification of these rare tumors.