Efeito adjuvante da propionibacterium acnes em vacina de células dendríticas na profilaxia e terapia do melanoma murino

• Ano de defesa: 2017
• Autor(a) principal: Ishimura, Mayari Eika [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Immunogenicity; Muridae; Propionibacterium acnes; Adjuvants, Immunologic; Cancer vaccines; Imunoterapêutica; Adjuvantes imunológicos; Vacinas anticâncer
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5015070; http://repositorio.unifesp.br/handle/11600/50681

Hybrid vaccines, which are vaccine models of total antigens expressed by a tumor cell combined with the ability of a dendritic cell (DC) to stimulate immune responses, have been investigated in clinical and experimental studies. However, the response triggered by these vaccines is often weak, requiring the use of adjuvants to increase vaccine immunogenicity. Killed Propionibacterium acnes (P. acnes) exerts immunomodulatory effects by increasing the phagocytic and tumoricidal activities of macrophages, promoting DC maturation, inducing pro-inflammatory cytokines production and increasing the humoral response to different antigens. Here, we evaluated the effect of P. acnes on a specific antitumor immune response elicited by a hybrid vaccine in a C57Bl/6 mouse model of melanoma. Two subcutaneous doses of a hybrid vaccine associated with P. acnes increased total IgG-, IgG1- and IgG2c-specific titers to B16F10 antigens, polarizing the humoral response to a T helper 1 (Th1) pattern. Concerning the cellular immune response, the absolute number of memory CD4 and CD8 T cells was increased. Moreover, cells cultured with tumor antigens exhibited increased IFN-γ secretion and reduced IL-4 expression by CD4 T cells, and CD8 T cells secreted larger amounts of IL-17 and IFN-γ. Furthermore, the addition of P. acnes to a hybrid vaccine increased the cytotoxic activity of splenocytes toward B16F10 in vitro and avoided late tumor progression in a pulmonary colonization model. These results revealed the adjuvant effect of a killed P. acnes suspension, as it improved specific humoral and cellular immune responses elicited by DC-tumor cell hybrid vaccines.