Influenza Virus Infection Elicits Protective Antibodies and T Cells Specific for Host Cell Antigens Also Expressed as Tumor-Associated Antigens: A New View of Cancer Immunosurveillance
Influenza Virus Infection Elicits Protective Antibodies and T Cells Specific for Host Cell Antigens Also Expressed as Tumor-Associated Antigens: A New View of Cancer Immunosurveillance
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DOI：
10.1158/2326-6066.cir-13-0125
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发表时间：
2014-03-01
影响因子：
10.1
通讯作者：
Finn, Olivera J.
中科院分区：
文献类型：
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作者：
Iheagwara, Uzoma K.;Beatty, Pamela L.;Finn, Olivera J.
大多数肿瘤相关抗原（TAA）是在癌细胞中异常表达的自分子，成为抗肿瘤免疫反应的靶标。在健康个体中发现了针对某些TAAs的抗体和T细胞，这些抗体和T细胞与降低患癌症的终生风险有关。患癌症的风险较低也与发热性病毒性疾病的病史有关。我们假设病毒感染可能导致异常形式的自我分子的短暂表达，其中一些是taa；在感染和炎症的辅助作用下，这些分子可以在对病毒抗原免疫的同时引发特异性抗体、T细胞和持久的免疫记忆。这种感染诱导的TAA免疫记忆有望为癌症提供终身免疫监测。以流感病毒感染小鼠作为模型系统，我们验证了这一假设，并证明流感经历的小鼠比感染初期的对照组小鼠更好地控制3LL小鼠的肺肿瘤攻击。利用2d凝胶电泳和质谱分析，我们在3LL肿瘤细胞上鉴定了许多分子，其中一些是已知的taa，这些分子被两次连续流感感染引发的抗体识别。我们详细研究了针对甘油醛-3-磷酸脱氢酶（GAPDH）、组蛋白H4、HSP90、苹果酸脱氢酶2和膜联蛋白A2的免疫应答，所有这些都在流感感染的肺部和肿瘤细胞中过表达。最后，我们表明，通过接种来自这些抗原的肽产生的免疫应答与肿瘤控制的改善相关。(c) 2013年aacr。
Most tumor-associated antigens (TAA) are self-molecules that are abnormally expressed in cancer cells and become targets of antitumor immune responses. Antibodies and T cells specific for some TAAs have been found in healthy individuals and are associated with lowered lifetime risk for developing cancer. Lower risk for cancer has also been associated with a history of febrile viral diseases. We hypothesized that virus infections could lead to transient expression of abnormal forms of self-molecules, some of which are TAAs; facilitated by the adjuvant effects of infection and inflammation, these molecules could elicit specific antibodies, T cells, and lasting immune memory simultaneously with immunity against viral antigens. Such infection-induced immune memory for TAA would be expected to provide life-long immune surveillance of cancer. Using influenza virus infection in mice as a model system, we tested this hypothesis and demonstrated that influenza-experienced mice control 3LL mouse lung tumor challenge better than infection-naive control mice. Using 2D-difference gel electrophoresis and mass spectrometry, we identified numerous molecules, some of which are known TAAs, on the 3LL tumor cells recognized by antibodies elicited by two successive influenza infections. We studied in detail immune responses against glyceraldehyde-3-phosphate dehydrogenase (GAPDH), histone H4, HSP90, malate dehydrogenase 2, and annexin A2, all of which were overexpressed in influenza-infected lungs and in tumor cells. Finally, we show that immune responses generated through vaccination against peptides derived from these antigens correlated with improved tumor control. (C) 2013 AACR.