Immunological background in paraneoplastic neurological syndrome and its therapeutic approach

副肿瘤神经综合征（PNS）属于自身免疫性神经疾病；在PNS中，肿瘤免疫和对神经元组织的自身免疫机制都被激发。由于肿瘤通常很小，常规筛查系统无法检测到，因此至少在PNS早期，抗肿瘤免疫可能会加速。此外，PNS发生在少数具有相似肿瘤病理的患者中，这表明PNS患者可能具有特殊的免疫背景，可以调节对肿瘤和神经组织的免疫。为了验证这一假设，我们分析了PNS患者外周血富含Treg的部分中淋巴细胞亚群的患病率以及FOXP3、TGF-pi、CTLA-4和GITR等功能分子的调节性T细胞（Treg） mRNA表达。结果显示，与无神经系统症状的癌症患者相比，PNS组FOXP3和CTLA-4 mRNA的表达降低，提示PNS在Treg系统功能障碍的癌症患者中发生。这些结果为理解PNS的病理机制和构建潜在癌症的治疗策略带来了新的见解。

Paraneoplastic neurological syndrome (PNS) is categorized in autoimmune neurological disease ; in that, cancer immunity and autoimmune mechanisms to neuronal tissue are both elicited in PNS. Because the tumor is often very small to be detected with conventional screening system, anti-tumor immunity might be accelerated at least in early stage of PNS. Furthermore, PNS develops in a small population of patients who have similar tumor pathology, suggesting that PNS patients might have special immunological backgrounds to tune up immunity on tumor and nervous tissue.To inspect this hypothesis, we analyzed prevalence of lymphocyte subpopulation and regulatory T cell (Treg) mRNA expression of functional molecules such as FOXP3, TGF-pi, CTLA-4 and GITR in Treg-rich fraction from peripheral blood of PNS patients.As the results, the expression of FOXP3 and CTLA-4 mRNA were diminished in PNS, group compared to cancer patients without neurological symptom, suggesting PNS develops in those cancer patients having dysfunction in Treg system. These results have brought a new insight in understanding the pathomechanisms of PNS and in constructing a treatment strategy for underlying cancer.