Expression of a soluble IL-10 receptor enhances the therapeutic effects of a papillomavirus-associated antitumor vaccine in a murine model

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2019-05, Vol.68 (5), p.753-763
• Main Authors: Silva, Jamile R., Sales, Natiely S., Silva, Mariângela O., Aps, Luana R. M. M., Moreno, Ana C. R., Rodrigues, Elaine G., Ferreira, Luís C. S., Diniz, Mariana O.
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Cancer; Cancer Research; Cancer Vaccines - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell activation; Cytotoxicity; DNA vaccines; Electroporation; Epithelial Cells - physiology; Glycoprotein D; Herpes simplex; Human papillomavirus; Human papillomavirus 16 - physiology; Immune Tolerance; Immunology; Immunotherapy; Immunotherapy - methods; Interleukin 10; Interleukin-10 - metabolism; Lymphocyte Activation; Lymphocytes T; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Neoplasms, Experimental - immunology; Oncology; Original; Original Article; Papillomavirus E7 Proteins - genetics; Papillomavirus Infections - immunology; Papillomavirus Vaccines - genetics; Papillomavirus Vaccines - immunology; Receptors, Interleukin-10 - genetics; Receptors, Interleukin-10 - immunology; Tumor cells; Tumors; Vaccines; Vaccines, DNA; Viral Envelope Proteins - genetics
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-018-02297-2

The presence of IL-10, produced either by tumor cells or immunosuppressive cells, is frequently associated with a poor prognosis for cancer progression. It may also negatively impact anticancer treatments, such as immunotherapies, that otherwise would promote the activation of cytotoxic T cells capable of detecting and destroying malignant cells. In the present study, we evaluated a new adjuvant approach for anticancer immunotherapy using a plasmid vector encoding a soluble form of the IL-10 receptor (pIL-10R). pIL-10R was coadministered to mice with a DNA vaccine encoding the type 16 human papillomavirus (HPV-16) E7 oncoprotein genetically fused with glycoprotein D of herpes simplex virus (HSV) (pgDE7h). Immunization regimens based on the coadministration of pIL-10R and pgDE7h enhanced the antitumor immunity elicited in mice injected with TC-1 cells, which express HPV-16 oncoproteins. The administration of the DNA vaccines by in vivo electroporation further enhanced the anticancer effects of the vaccines, leading to the activation of tumor-infiltrating polyfunctional E7-specific cytotoxic CD8 + T cells and control of the expansion of immunosuppressive cells. In addition, the combination of immunotherapy and pIL-10R allowed the control of tumors in more advanced growth stages that otherwise would not be treatable by the pgDE7h vaccine. In conclusion, the proposed treatment involving the expression of IL-10R enhanced the antitumor protective immunity induced by pgDE7h administration and may contribute to the development of more efficient clinical interventions against HPV-induced tumors.