Experimental oncology

Immuno-biotherapy of melanoma and solid tumors

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Head of Unit

Vincenzo Russo

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Treatment options for patients affected by advanced-stage metastatic tumors (melanoma, lung cancer, kidney cancer, etc.) have changed dramatically in the past six years, with the approval of new antitumor therapies based on the stimulation of the immune system. These treatments have indeed increased the overall survival of patients affected by histologically different tumors (melanoma, lung tumors, etc.). However, there are still many patients relapsing after an initial clinical benefit. Therefore, there is an urgent need to identify new evasion mechanisms adopted by tumors to escape immune cells, in order to increase the efficacy of antitumor treatments. The research activity of the Unit of immuno- biotherapy of melanoma and solid tumors is focused on the investigation of new tumor immune escape mechanisms.

Research activity

This group has recently identified an escape mechanism based on the release of cholesterol metabolites (i.e. oxysterols) by tumors of different hystotypes. Oxysterols and their receptors (Liver X Receptors), primarily identified as regulators of cholesterol homeostasis, are currently recognized as integrators of metabolic and inflammatory signaling. Recent studies have shown that tumor-derived oxysterols inhibit the antitumor immune response by dampening cells involved in the presentation of tumor antigens (dendritic cells), and by recruiting neutrophils endowed with pro- tumor capabilities within the tumor microenvironment. Neutrophils favor tumor growth by promoting the formation of new blood vessels or by suppressing lymphocytes recognizing tumor antigens.
Currently, the unit is investigating the cellular and molecular mechanisms by which oxysterols are generated and inactivated during the inflammation associated to cancer.
In addition, researchers of this group are characterizing, in different tumor models, molecules interfering with the LXR/oxysterol axis in order to potentiate antitumor immune responses.