Oral administration of lipoteichoic acid from Lactobacillus rhamnosus GG overcomes UVB‐induced immunosuppression and impairs skin tumor growth in mice

• Published in: European journal of immunology 2019-11, Vol.49 (11), p.2095-2102
• Main Authors: Friedrich, Adrián D., Campo, Valeria E., Cela, Eliana M., Morelli, Adrian E., Shufesky, William J., Tckacheva, Olga A., Leoni, Juliana, Paz, Mariela L., Larregina, Adriana T., González Maglio, Daniel H.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Antitumor activity; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Cell Movement - drug effects; Cell Movement - immunology; Cell Movement - radiation effects; Contact dermatitis; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - pathology; Dendritic Cells - radiation effects; Dermatitis, Contact - genetics; Dermatitis, Contact - immunology; Dermatitis, Contact - pathology; Female; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - immunology; Gastrointestinal Tract - pathology; Gastrointestinal Tract - radiation effects; Homing; Hypersensitivity; Immune system; Immunosuppression; Lactobacillus rhamnosus; Lactobacillus rhamnosus - chemistry; Lipopolysaccharides - isolation & purification; Lipopolysaccharides - pharmacology; Lipoteichoic acid; Lymph nodes; Lymph Nodes - drug effects; Lymph Nodes - immunology; Lymph Nodes - pathology; Lymph Nodes - radiation effects; Mice; Mice, Inbred C57BL; Oral administration; Phenotypes; probiotics; Skin; Skin - drug effects; Skin - immunology; Skin - pathology; Skin - radiation effects; Skin cancer; skin diseases; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Squamous cell carcinoma; Teichoic Acids - isolation & purification; Teichoic Acids - pharmacology; tolerance; Tumors; Ultraviolet radiation; Ultraviolet Rays - adverse effects; UV radiation
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201848024

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. Oral administration of LTA overcomes UVB‐induced immunosuppression, through increased dendritic cell homing to lymph nodes, the consequent T cell priming and, finally, CD8+ effector T cell recruitment to challenged skin. Moreover, LTA is able to reduce the growth of established UVB‐induced skin tumors.