Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events.
Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events.
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DOI：
10.1186/s40425-018-0353-7
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发表时间：
2018-05-22
影响因子：
10.9
通讯作者：
Rothschild SI
中科院分区：
文献类型：
--
作者：
Läubli H;Balmelli C;Kaufmann L;Stanczak M;Syedbasha M;Vogt D;Hertig A;Müller B;Gautschi O;Stenner F;Zippelius A;Egli A;Rothschild SI
免疫检查点抑制抗体被引入癌症患者的常规临床实践中。检查点阻断导致一些患者的持久缓解，但也可能诱导免疫相关不良事件（irAE）。肺癌患者在感染流感病毒时，并发症的风险增加。因此，建议接种疫苗。然而，检查点封锁期间流感疫苗接种的有效性和安全性及其对irAE的影响尚不清楚。同样，在PD-1阻断期间，疫苗接种对患者T细胞介导的免疫反应的影响仍然不清楚。我们使用三价灭活流感疫苗接种了23名肺癌患者和11名年龄匹配的健康对照，以研究检查点封锁期间疫苗诱导的免疫力和安全性。我们没有观察到患者和健康对照组在疫苗诱导的针对所有三种病毒抗原的抗体滴度方面的显著差异。流感疫苗接种在超过60%的患者/参与者中产生保护滴度。在癌症患者中，疫苗接种后irAE的频率为52.2%，至发生的中位时间为疫苗接种后3.2个月。23例患者中有6例（26.1%）显示重度3/4级irAE。irAE的频率可能高于文献中先前发表的发生率和我们机构非研究人群中观察到的发生率（所有等级25.5%，3/4级9.8%）。虽然这是一项非随机试验，患者数量有限，但免疫毒性发生率增加令人担忧。这一发现应在更大的患者人群中进行研究。
Immune checkpoint inhibiting antibodies were introduced into routine clinical practice for cancer patients. Checkpoint blockade has led to durable remissions in some patients, but may also induce immune-related adverse events (irAEs). Lung cancer patients show an increased risk for complications, when infected with influenza viruses. Therefore, vaccination is recommended. However, the efficacy and safety of influenza vaccination during checkpoint blockade and its influence on irAEs is unclear. Similarly, the influence of vaccinations on T cell-mediated immune reactions in patients during PD-1 blockade remains poorly defined. We vaccinated 23 lung cancer patients and 11 age-matched healthy controls using a trivalent inactivated influenza vaccine to investigate vaccine-induced immunity and safety during checkpoint blockade. We did not observe significant differences between patients and healthy controls in vaccine-induced antibody titers against all three viral antigens. Influenza vaccination resulted in protective titers in more than 60% of patients/participants. In cancer patients, the post-vaccine frequency of irAEs was 52.2% with a median time to occurrence of 3.2 months after vaccination. Six of 23 patients (26.1%) showed severe grade 3/4 irAEs. This frequency of irAEs might be higher than the rate previously published in the literature and the rate observed in a non-study population at our institution (all grades 25.5%, grade 3/4 9.8%). Although this is a non-randomized trial with a limited number of patients, the increased rate of immunological toxicity is concerning. This finding should be studied in a larger patient population.
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T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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影响因子：
50.5
作者：
Hajjar, L. A.;Mauad, T.;Hoff, P. M.
通讯作者：
Hoff, P. M.
DOI：
10.1016/s1470-2045(17)30421-7
发表时间：
2017-08
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Harrington KJ;Ferris RL;Blumenschein G Jr;Colevas AD;Fayette J;Licitra L;Kasper S;Even C;Vokes EE;Worden F;Saba NF;Kiyota N;Haddad R;Tahara M;Grünwald V;Shaw JW;Monga M;Lynch M;Taylor F;DeRosa M;Morrissey L;Cocks K;Gillison ML;Guigay J
通讯作者：
Guigay J
增强的抗肿瘤免疫力需要常驻记忆CD8+T细胞和循环记忆CD8+T细胞之间的相互作用。
影响因子：
16.6
作者：
Enamorado M;Iborra S;Priego E;Cueto FJ;Quintana JA;Martínez-Cano S;Mejías-Pérez E;Esteban M;Melero I;Hidalgo A;Sancho D
通讯作者：
Sancho D
影响因子：
2.6
作者：
Dirks, J.;Egli, A.;Hirsch, H. H.
通讯作者：
Hirsch, H. H.