Patard J J, Guillé F, Lobel B, Abbou C C, Chopin D
Service d'Urologie, Hôpital Pontchaillou, Rennes, France.
Prog Urol. 1998 Jun;8(3):415-21.
The better understanding of antitumour immunity has improved our knowledge concerning the mechanisms of action of BCG. There are three phases in the immune response to BCG: first of all, BCG adheres and is then phagocytosed by antigen-presenting cells, but also by urothelial cells. This phase corresponds to the early release of so-called inflammatory cytokines (IL-1, IL-6, IL-8). These cytokines may be responsible for certain adverse effects, but may also participate in the cytotoxic phenomenon. The second phase consists of recognition of bacterial antigens by CD4 lymphocytes, which release mainly IL-2 and IFN-gamma(TH1 response). This cell activation leads to the third phase, which consists of amplification of cytotoxic-populations: CD8, gamma delta lymphocytes, macrophages, NK, LAK, BAK. All these cells also release cytokines which then regulate the response. The identification of these modulations allows rationalization of BCG instillation protocols, but identification of the truly cytotoxic elements would allow the proposal of more effective immunization protocols.
对抗肿瘤免疫的深入了解增进了我们对卡介苗作用机制的认识。对卡介苗的免疫反应有三个阶段:首先,卡介苗黏附并随后被抗原呈递细胞吞噬,尿路上皮细胞也可吞噬。此阶段对应所谓炎性细胞因子(白细胞介素-1、白细胞介素-6、白细胞介素-8)的早期释放。这些细胞因子可能是某些不良反应的原因,但也可能参与细胞毒性现象。第二阶段包括CD4淋巴细胞对细菌抗原的识别,其主要释放白细胞介素-2和干扰素-γ(TH1反应)。这种细胞活化导致第三阶段,即细胞毒性群体的扩增:CD8、γδ淋巴细胞、巨噬细胞、自然杀伤细胞、淋巴因子激活的杀伤细胞、卡介苗激活的杀伤细胞。所有这些细胞也释放细胞因子,进而调节免疫反应。对这些调节的识别有助于卡介苗灌注方案的合理化,但确定真正的细胞毒性成分将有助于提出更有效的免疫方案。