Institut National de Santé et de Recherche Médicale (INSERM), UMRS872, Centre de Recherche des Cordeliers, Paris, France.
Clin Exp Immunol. 2011 Sep;165(3):329-37. doi: 10.1111/j.1365-2249.2011.04416.x. Epub 2011 Jun 10.
A large body of evidence indicates that the immune microenvironment controls tumour development. Primary central nervous system lymphomas (PCNSL) are aggressive tumours growing in the central nervous system (CNS). To evaluate the role and characteristics of this immune-privileged site in anti-tumour defences, we compared the cellular and molecular immune microenvironments of growing murine lymphoma B cells injected into the brain or the spleen. In the brain, immune cells, including dendritic cells and T lymphocytes with a large proportion of CD4(+) forkhead box P3 (FoxP3(+)) regulatory T cells, rapidly infiltrated the tumour microenvironment. These populations also increased in number in the spleen. The T cell cytokine profiles in tumour-bearing mice were similar in the two sites, with predominant T helper type 1 (Th1)/Th17 polarization after polyclonal stimulation, although some interleukin (IL)-4 could also be found. We demonstrated that these T cells have anti-tumour activity in the CNS, although less than in the spleen: nude mice that received lymphoma cells intracerebrally died significantly earlier than immunocompetent animals. These results demonstrate that the brain is able to recruit all the major actors to mount a specific anti-tumour immune response against lymphoma.
大量证据表明,免疫微环境控制着肿瘤的发展。原发性中枢神经系统淋巴瘤(PCNSL)是一种在中枢神经系统(CNS)中生长的侵袭性肿瘤。为了评估这个免疫特权部位在抗肿瘤防御中的作用和特征,我们比较了注射到大脑或脾脏中的生长中的鼠淋巴瘤 B 细胞的细胞和分子免疫微环境。在大脑中,包括树突状细胞和 T 淋巴细胞在内的免疫细胞迅速浸润肿瘤微环境,其中很大一部分是 CD4(+)叉头框 P3(FoxP3(+))调节性 T 细胞。这些细胞群在脾脏中的数量也增加了。在两个部位,荷瘤小鼠的 T 细胞细胞因子谱相似,在多克隆刺激后表现出主要的辅助性 T 细胞 1(Th1)/Th17 极化,尽管也可以发现一些白细胞介素(IL)-4。我们证明这些 T 细胞在中枢神经系统中具有抗肿瘤活性,尽管不如在脾脏中那么强:接受脑内淋巴瘤细胞的裸鼠比免疫功能正常的动物死亡明显更早。这些结果表明,大脑能够招募所有主要的参与者来针对淋巴瘤产生特异性的抗肿瘤免疫反应。