Impaired CD8+ T-Cell Reactivity against Viral Antigens in Cancer Patients with Solid Tumors
Impaired CD8+ T-Cell Reactivity against Viral Antigens in Cancer Patients with Solid Tumors
复制标题
实体瘤癌症患者 CD8 T 细胞针对病毒抗原的反应性受损
DOI：
10.1007/s15010-004-3140-y
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发表时间：
2004
期刊：
影响因子：
7.5
通讯作者：
R. Speck
中科院分区：
文献类型：
--
作者：
A. Trojan;R. Giger;N. Rist;R. Speck
摘要背景：血液恶性肿瘤患者发生各种感染的风险增加。在实体癌患者中，描述了影响 T 细胞反应的多种免疫抑制机制。我们假设晚期实体瘤患者可能表现出对病毒抗原的识别受损。为了测试这一点，比较了患者和健康个体中 CD8+ T 细胞识别流感和痘苗病毒记忆抗原的能力。由于所有患者和大多数健康个体多年前都接种了痘苗疫苗，因此两组的比较预计将在不同的效应 T 细胞反应性方面提供特别丰富的信息。 材料和方法：我们的测试人群包括 16 名健康个体和 12 名目前未接受化疗的晚期实体癌患者。我们用充分表征的甲型流感基质 58-66 肽和源自改良痘苗病毒安卡拉 (MVA) 的免疫原性和 HLA-A*0201 限制性肽表位 SLSAYIIRV 离体刺激外周血单核细胞 (PBMC)。通过定量实时聚合酶链式反应 (qRT-PCR) 测量干扰素 γ (IFN-γ) mRNA 表达水平的变化来确定特定的 CD8+ T 细胞反应性。结果：我们发现，与健康个体相比，表现出对牛痘表位的特定 T 细胞识别的癌症患者明显较少（分别为 25% 和 69%）。此外，癌症患者中针对两种病毒肽的 T 细胞反应强度显着降低。结论：晚期肿瘤患者不太可能针对病毒表位产生 T 细胞反应。这些发现可能对针对病毒引起的疾病（包括肿瘤）的免疫治疗干预措施的设计具有影响。
Abstract.Background:Patients with hematological malignancies are at increased risk for various infections. In patients with solid cancer, a variety of immunosuppressive mechanisms affecting T-cell response are described. We hypothesized that patients with advanced solid tumors may exhibit an impaired recognition of viral antigens. To test this, the capability of CD8+ T cells to recognize recall antigens from influenza and vaccinia virus was compared in patients and healthy individuals. Since all patients and most of the healthy individuals had been vaccinated against vaccinia years ago, comparison of the two groups was expected to be especially informative with respect to distinct effector T-cell reactivity.Materials and Methods:Our test population included 16 healthy individuals and 12 patients with advanced solid cancers who were currently not receiving chemotherapy. We stimulated peripheral blood mononuclear cells (PBMC) ex vivo with the well-characterized influenza A matrix 58–66 peptide and the immunogenic and HLA-A*0201 restricted peptide epitope SLSAYIIRV derived from the modified vaccinia virus Ankara (MVA). A specific CD8+ T-cell reactivity was determined by quantitative real-time polymerase chain reaction (qRT-PCR) measuring changes in interferon gamma (IFN-γ) mRNA expression levels.Results:We found that significantly fewer cancer patients than healthy individuals exhibited specific T-cell recognition of the vaccinia epitope (25% and 69%, respectively). In addition, strength of the T-cell responses against both viral peptides was significantly reduced in cancer patients.Conclusion:Patients with advanced tumors are less likely to mount a T-cell response against viral epitopes. These findings may have implications for the design of immunotherapeutic interventions against virus-induced diseases, including tumors.
影响因子：
4.4
作者：
Grayson, JM;Murali-Krishna, K;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
4.4
作者：
Sherven P Sharma;M. Stolina;Ying Q Lin;B. Gardner;Patrice W. Miller;M. Kronenberg;S. Dubinett
通讯作者：
Sherven P Sharma;M. Stolina;Ying Q Lin;B. Gardner;Patrice W. Miller;M. Kronenberg;S. Dubinett
影响因子：
6.4
作者：
Ennis, FA;Cruz, J;McClain, DJ
通讯作者：
McClain, DJ