非抗肿瘤IgG4对肿瘤免疫抑制作用的研究

我团队在前期实验中取得了一个重要的发现，即肿瘤微环境中IgG的一个亚型IgG4明显升高， 且升高的程度与肿瘤预后相关，而这种升高的IgG4并不抗肿瘤抗原，我们的结果提示，这种非抗肿瘤的IgG4可能在肿瘤微的环境中起到阻断免疫细胞和抗体对肿瘤的识别和杀伤作用，我们因此提出了“IgG4是肿瘤免疫阻断剂”的假说。本研究将对这一假说进行深入系统的研究，我们计划在当地高发的四种实体肿瘤（食道癌，肺癌，结直肠癌和乳腺癌）中对这一假说进行验证，揭示IgG4如何阻断肿瘤免疫反应，研究其生理病理机制和意义。我们将采用体液和细胞免疫模型（ADCC、ADCP和CDC等），以及生化、免疫和分子生物学技术开展试验，并在动物肿瘤模型中将这一理论进行验证。这项研究将可能为肿瘤的免疫治疗开辟一条新的途径。

Recently our research team made an important discovery and found that a subclass of IgG, IgG4 was significantly increased in the serum of cancer patients and cancer microenvironment. This increase was correlated to cancer malignancy and patients prognosis. We also found that the increased IgG4 was not specific for cancer. Preliminary results suggest that such non-cancer-specific IgG4 may block the local immune response against cancer. We therefore formulated a hypothesis “non-cancer-specific IgG4 is a blocker of immune response against cancer”. We aim to verify this hypothesis with the proposed study and employ four solid cancer types (esophageal, lung, colon and breast) to investigate the mechanism and pathophysiological significance of this phenomenon. We will employ the classic ADCC, ADCP and CDC immune response models and using biochemistry, immunology and molecular biology techniques to perform this study. We will also use mouse animal models to study the possible promoting and inhibitory effects of IgG4 on cancer growth and metastasis. This research aims to establish a new approach to cancer therapy.