Platzer Barbara, Elpek Kutlu G, Cremasco Viviana, Baker Kristi, Stout Madeleine M, Schultz Cornelia, Dehlink Eleonora, Shade Kai-Ting C, Anthony Robert M, Blumberg Richard S, Turley Shannon J, Fiebiger Edda
Division of Gastroenterology and Nutrition, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Cell Rep. 2015 Mar 10;10(9):1487-1495. doi: 10.1016/j.celrep.2015.02.015. Epub 2015 Mar 5.
Epidemiologic studies discovered an inverse association between immunoglobulin E (IgE)-mediated allergies and cancer, implying tumor-protective properties of IgE. However, the underlying immunologic mechanisms remain poorly understood. Antigen cross-presentation by dendritic cells (DCs) is of key importance for anti-tumor immunity because it induces the generation of cytotoxic CD8 T lymphocytes (CTLs) with specificity for tumor antigens. We demonstrate that DCs use IgE and FcεRI, the high-affinity IgE receptor, for cross-presentation and priming of CTLs in response to free soluble antigen at low doses. Importantly, IgE/FcεRI-mediated cross-presentation is a distinct receptor-mediated pathway because it does not require MyD88 signals or IL-12 induction in DCs. Using passive immunization with tumor antigen-specific IgE and DC-based vaccination experiments, we demonstrate that IgE-mediated cross-presentation significantly improves anti-tumor immunity and induces memory responses in vivo. Our findings suggest a cellular mechanism for the tumor-protective features of IgE and expand the known physiological functions of this immunoglobulin.
流行病学研究发现，免疫球蛋白E（IgE）介导的过敏反应与癌症之间存在负相关，这意味着IgE具有肿瘤保护特性。然而，其潜在的免疫机制仍知之甚少。树突状细胞（DC）的抗原交叉呈递对于抗肿瘤免疫至关重要，因为它能诱导产生对肿瘤抗原有特异性的细胞毒性CD8 T淋巴细胞（CTL）。我们证明，DC利用IgE和高亲和力IgE受体FcεRI，在低剂量游离可溶性抗原存在的情况下进行交叉呈递并启动CTL。重要的是，IgE/FcεRI介导的交叉呈递是一种独特的受体介导途径，因为它不需要DC中的MyD88信号或IL-12诱导。通过使用肿瘤抗原特异性IgE的被动免疫和基于DC的疫苗接种实验，我们证明IgE介导的交叉呈递显著增强了抗肿瘤免疫力，并在体内诱导了记忆反应。我们的研究结果揭示了IgE肿瘤保护特性的细胞机制，并扩展了这种免疫球蛋白已知的生理功能。
