Disciplina de Imunologia, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, Brazil.
Laboratório de Imunobiologia do Cancer, Disciplina de Biologia Celular, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, Brazil.
PLoS One. 2018 Oct 9;13(10):e0205148. doi: 10.1371/journal.pone.0205148. eCollection 2018.
Hybrid vaccines have been investigated in clinical and experimental studies once expresses total antigens of a tumor cell combined with the ability of a dendritic cell (DC) to stimulate immune responses. 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 mouse melanoma model. Hybrid vaccine associated with P. acnes increased the absolute number of memory T cells, the IFN-γ secretion by these cells and the IgG-specific titers to B16F10 antigens, polarizing the immune response to a T helper 1 pattern. 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.
杂交疫苗已在临床和实验研究中进行了研究,这些疫苗表达了肿瘤细胞的总抗原,结合树突状细胞(DC)刺激免疫反应的能力。然而,这些疫苗引发的反应通常较弱,需要使用佐剂来提高疫苗的免疫原性。已死痤疮丙酸杆菌(P. acnes)通过增加巨噬细胞的吞噬和杀肿瘤活性、促进 DC 成熟、诱导促炎细胞因子产生以及增加对不同抗原的体液反应,发挥免疫调节作用。在这里,我们在小鼠黑色素瘤模型中评估了 P. acnes 对杂交疫苗引起的特定抗肿瘤免疫反应的影响。与 P. acnes 相关的杂交疫苗增加了记忆 T 细胞的绝对数量、这些细胞的 IFN-γ 分泌以及针对 B16F10 抗原的 IgG 特异性滴度,使免疫反应向 Th1 模式极化。此外,向杂交疫苗中添加 P. acnes 可增加脾细胞对 B16F10 的体外细胞毒性活性,并避免肺定植模型中的晚期肿瘤进展。这些结果揭示了已死 P. acnes 悬浮液的佐剂作用,因为它改善了由 DC-肿瘤细胞杂交疫苗引起的特异性体液和细胞免疫反应。