The shaping of a polyvalent and highly individual T-cell repertoire in the bone marrow of breast cancer patients
The shaping of a polyvalent and highly individual T-cell repertoire in the bone marrow of breast cancer patients
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DOI：
10.1158/0008-5472.can-05-4201
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发表时间：
2006-08-15
期刊：
影响因子：
11.2
通讯作者：
Beckhove, Philipp
中科院分区：
文献类型：
--
作者：
Sommerfeldt, Nora;Schuetz, Florian;Beckhove, Philipp
我们通过短期 IFN-γ 酶联免疫斑点 (ELISpot) 分析，分析了 39 名原发性手术乳腺癌患者和 11 名健康女性捐献者骨髓中的 T 细胞库，以了解自发诱导的效应/记忆 T 淋巴细胞的存在和频率，这些淋巴细胞对 10 种乳腺肿瘤相关抗原 (TAA) 和 3 种正常乳腺组织相关抗原具有肽-HLA-A2 限制性反应。 67% 的患者识别出 TAA 的平均频率为每 106 个 T 细胞有 144 个 TAA 反应细胞。这些患者平均同时识别出 47% 的测试 TAA。 T 细胞库是高度多价的，并且在每位患者识别的 TAA 模式上表现出明显的个体差异。TAA 之间的反应性存在强烈差异，范围从 100% 识别前列腺特异性抗原 (p141-149) 到仅 25% 识别 MUC1(p12-20) 或 Her-2/neu(p369-377)。与 TAA 相比，正常乳腺组织相关抗原的反应性患者比例 (30%) 和识别抗原 (27%) 较低，T 细胞的平均频率仅为 85/10(6)。健康个体也含有 TAA 反应性 T 细胞，但这种细胞库受到更多限制，并且频率与对正常乳腺组织相关抗原反应的 T 细胞处于同一范围内。我们的数据显示了乳腺癌患者识别 TAA 的高度个体化的 T 细胞库。这对于 T 细胞免疫诊断、肿瘤疫苗设计和预测免疫反应具有潜在的相关性。
We analyzed the T-cell repertoires from the bone marrow of 39 primary operated breast cancer patients and 11 healthy female donors for the presence and frequencies of spontaneously induced effector/memory T lymphocytes with peptide-HLA-A2-restricted reactivity against 10 breast tumor-associated antigens (TAA) and 3 normal breast tissue-associated antigens by short-term IFN-gamma enzyme-linked inummospot (ELISpot) analysis. Sixty-seven percent of the patients recognized TAAs with a mean frequency of 144 TAA reactive cells per 106 T cells. These patients recognized simultaneously an average of 47% of the tested TAAs. The T-cell repertoire was highly polyvalent and exhibited pronounced interindividual differences in the pattern of TAAs recognized by each patient., Strong differences of reactivity were noticed between TAAs, ranging from 100% recognition of prostate-specific antigen(p141-149) to only 25% recognition of MUC1(p12-20) or Her-2/neu(p369-377). In comparison with TAAs reactivity to normal breast tissue-associated antigens was lower with respect to the proportions of responding patients (30%) and recognized antigens (27%), with a mean frequency of only 85/10(6) T cells. Healthy individuals also contained TAA-reactive T cells but this repertoire was more restricted and the frequencies were in the same range as T cells reacting to normal breast tissue-associated antigens. Our data show a highly individual T-cell repertoire for recognition of TAAs in breast cancer patients. This has potential relevance for T-cell immune diagnostics, for tumor vaccine design, and for predicting immune responsiveness.