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Such a combined preoperative chemioradiotherapy and oxaliplatin-containing regimen is well tolerated with non increase in surgical toxicity. The good response rate observed warrants its use in further clinical trials.

The abscopal effect (AbE) is defined as radiation-induced shrinkage of distant, non-treated, neoplastic lesions and it is considered the best clinical picture of the efficient immune stimulation by irradiation. The first report about abscopal tumor regression upon radiotherapy dates back to the beginning of the 20th century. The growing preclinical and clinical synergism between radiation and immunotherapy gave birth the purpose to more easily reproduce the abscopal effect, nevertheless, it is still rare in clinical practice. In this review we summarize immunological modulation of radiotherapy, focusing on the well-balanced equilibrium of tumor microenvironment and how radio-immunotherapy combinations can perturb it, with particular attention on head and neck squamous cell cancer. Finally, we investigate future perspectives, with the aim to “tailor” the abscopal effect to the patient.

Glioblastoma multiforme (GBM) is a fatal brain tumor without effective drug treatment. In this study, we highlight, for the first time, the contribution of chromatin remodeling gene Lysine (K)-specific demethylase 5C (KDM5C) in GBM via an extensive analysis of clinical, expression, and functional data, integrated with publicly available omic datasets. The expression analysis on GBM samples (N = 37) revealed two informative subtypes, namely KDM5CHigh and KDM5CLow, displaying higher/lower KDM5C levels compared to the controls. The former subtype displays a strong downregulation of brain-derived neurotrophic factor (BDNF)—a negative KDM5C target—and a robust overexpression of hypoxia-inducible transcription factor-1A (HIF1A) gene, a KDM5C modulator. Additionally, a significant co-expression among the prognostic markers HIF1A, Survivin, and p75 was observed. These results, corroborated by KDM5C overexpression and hypoxia-related functional assays in T98G cells, suggest a role for the HIF1A-KDM5C axis in the hypoxic response in this tumor. Interestingly, fluorescence-guided surgery on GBM sections further revealed higher KDM5C and HIF1A levels in the tumor rim niche compared to the adjacent tumor margin, indicating a regionally restricted hyperactivity of this regulatory axis. Analyzing the TCGA expression and methylation data, we found methylation changes between the subtypes in the genes, accounting for the hypoxia response, stem cell differentiation, and inflammation. High NANOG and IL6 levels highlight a distinctive stem cell-like and proinflammatory signature in the KDM5CHigh subgroup and GBM niches. Taken together, our results indicate HIF1A-KDM5C as a new, relevant cancer axis in GBM, opening a new, interesting field of investigation based on KDM5C as a potential therapeutic target of the hypoxic microenvironment in GBM.