Influência do eixo inibitório PD-1/PD-L1 em diferentes aspectos da resposta imune anti-tumoral e anti-viral

• Ano de defesa: 2019
• Autor(a) principal: Gassen, Rodrigo Benedetti
• Orientador(a): Souza, Ana Paula Duarte de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul
• Programa de Pós-Graduação: Programa de Pós-Graduação em Medicina/Pediatria e Saúde da Criança
• Departamento: Escola de Medicina
• País: Brasil
• Palavras-chave em Português: Tumor; Vírus Sincicial Respiratório; PD-1/ PD-L1; Células Dendríticas; Células T CD4 Foliculares; Imunoterapia; IL-21
• Palavras-chave em Inglês: Tumor; Respiratory Syncytial Virus; Dendritic Cells; T Follicular Helper Cells; Immunotherapy
• Área do conhecimento CNPq: CIENCIAS DA SAUDE::MEDICINA
• Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/8435

To maintain homeostasis after activation and memory formation, some immune cells either die or are deactivated by the expression of various molecules. The PD-1 / PD-L1 axis is an important inhibitory pathway involved in regulating immune responses. Increased expression of these inhibitory molecules is a strategy used by tumors and even some viruses to evade the immune response. In the first part of the study, used a melanoma model to investigate whether, upon treatment with anti-PD1 antibody, an early activation of dendritic cell subpopulations (DCs) and T cells could be observed in blood or draining lymph nodes (DLN) and correlate with inhibition of tumor growth. In the second part of the study, we hypothesized that Respiratory Syncytial Virus (VSR) modulates follicular CD4 + T cells (TFH) and thus decreases the affinity of the responding antibodies by increasing PD-L1 expression. In the tumor model, the results indicate that treatment with anti-PD-1 can affect not only T cells, but also subpopulations of DCs. This can be observed in the blood, providing relevant information to predict early responses to this immunotherapeutic. In the case of the viral model, PD-L1 blockade led to increased IL-21 expression, activating the entire humoral immune response and controlling VSR infection. Our results stress the importance of the PD-1 / PD-L1 signaling axis as a common pathway activated by inhibition of immune responses in both infection and tumor growth.