Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
J Autoimmun. 2014 Nov;54:112-7. doi: 10.1016/j.jaut.2014.05.002. Epub 2014 Jun 10.
Here, I consider how benign autoimmunity, the immunological homunculus, can be used to reinstate the healthy regulation of inflammation in both autoimmune diseases and in tumor immunotherapy. Different autoimmune diseases manifest clinically distinct phenotypes, but, in general, they all result from the transition of benign, healthy recognition of key body molecules into a damaging effector reaction. Tumors, in contrast to autoimmune diseases, grow by subverting the immune system into supporting and protecting the growing tumor from immune surveillance. Therefore our therapeutic aim in autoimmune disease is to induce the immune system to down-regulate the specific autoimmune effector reaction that causes the disease; in tumor immunotherapy, on the contrary, we aim to deprive the growing tumor of its illicit activation of immune suppression and to unleash an autoimmune disease targeted to the tumor. The recent success of anti-PD1 and anti-CTLR4 treatments exemplify the reinstatement of tumor autoimmunity subsequent to inhibition of immune suppression. With regard to the therapy of autoimmune diseases, I cite examples of immune system down-regulation of autoimmune diseases by T cell vaccination or HSP60 peptide treatment. Inducing the immune system to regulate itself is safer than global immune suppression and may be more effective in the long run.
在这里，我考虑了良性自身免疫、免疫同形物如何被用来恢复自身免疫性疾病和肿瘤免疫治疗中炎症的健康调节。不同的自身免疫性疾病在临床上表现出不同的表型，但总的来说，它们都是由于对关键身体分子的良性、健康识别转变为破坏性效应反应而引起的。与自身免疫性疾病不同，肿瘤通过颠覆免疫系统来支持和保护生长中的肿瘤免受免疫监视而生长。因此，我们在自身免疫性疾病中的治疗目标是诱导免疫系统下调导致疾病的特定自身免疫效应反应；相反，在肿瘤免疫治疗中，我们的目标是剥夺生长中的肿瘤对免疫抑制的非法激活，并释放针对肿瘤的自身免疫性疾病。最近抗 PD-1 和抗 CTLA-4 治疗的成功例证说明了抑制免疫抑制后肿瘤自身免疫的恢复。关于自身免疫性疾病的治疗，我引用了通过 T 细胞疫苗接种或 HSP60 肽治疗来下调自身免疫性疾病的免疫系统的例子。诱导免疫系统自我调节比全身免疫抑制更安全，从长远来看可能更有效。
