Assuntos
Metformina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Lesões Experimentais por Radiação/prevenção & controle , Radiodermite/prevenção & controle , Proteína Supressora de Tumor p53/metabolismo , Aldeídos/metabolismo , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/imunologia , Carcinogênese/efeitos da radiação , Dano ao DNA/imunologia , Dano ao DNA/efeitos da radiação , Feminino , Humanos , Melanoma/etiologia , Melanoma/patologia , Melanoma/prevenção & controle , Metformina/uso terapêutico , Camundongos , Estresse Oxidativo/genética , Estresse Oxidativo/imunologia , Lesões Experimentais por Radiação/imunologia , Lesões Experimentais por Radiação/patologia , Radiodermite/imunologia , Radiodermite/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologia , Pele/efeitos da radiação , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/prevenção & controle , Tirosina/análogos & derivados , Tirosina/metabolismo , Raios Ultravioleta/efeitos adversosRESUMO
There is increasing evidence of the relevant connection and regulation between the gut and skin immune axis. In fact, oral administration of lipoteichoic acid (LTA) from Lactobacillus rhamnosus GG (LGG) prevents the development of UV-induced skin tumors in chronically exposed mice. Here we aim to evaluate whether this LTA is able to revert UV-induced immunosuppression as a mechanism involved in its anti-tumor effect and whether it has an immunotherapeutic effect against cutaneous squamous cell carcinoma. Using a mouse model of contact hypersensitivity, we demonstrate that LTA overcomes UV-induced skin immunosuppression. This effect was in part achieved by modulating the phenotype of lymph node resident dendritic cells (DC) and the homing of skin migratory DC. Importantly, oral LTA reduced significantly the growth of established skin tumors once UV radiation was discontinued, demonstrating that it has a therapeutic, besides the already demonstrated preventive antitumor effect. The data presented here strongly indicates that oral administration of LTA represents a promising immunotherapeutic approach for different conditions in which the skin immune system is compromised.