T cell responses in early-stage melanoma patients occur frequently and are not associated with humoral response

T cell responses in early-stage melanoma patients occur frequently and are not associated with humoral response
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早期黑色素瘤患者的 T 细胞反应频繁发生,且与体液反应无关

DOI:
10.1007/s00262-015-1739-8
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发表时间:
2015
期刊:
Cancer Immunology, Immunotherapy
影响因子:
--
通讯作者:
Beckhove P
Beckhove P
中科院分区:
--
文献类型:
--
作者:
Pfirschke C;Gebhardt C;Zörnig I;Pritsch M;Eichmüller SB;Jäger D;Beckhove P

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在包括恶性黑色素瘤(MM)在内的不同肿瘤类型的患者中均可检测到内源性肿瘤特异性T细胞。它们可以控制肿瘤生长,影响患者生存,并与改善免疫检查点治疗的临床反应相关。因此,它们可能代表了各自治疗决策的有效生物标志物。到目前为止,内源性mm反应性T细胞的主要靶抗原尚未系统确定。相反,我们讨论自身抗体作为mm特异性T细胞的替代参数。因此,在肿瘤切除后60多天的时间里,我们通过IFNγ ELISpot和基于珠状荧光的多重测定法确定了38名非转移性原发性MM患者和健康个体的自发T细胞和体液反应的主要靶抗原,并使用广泛的MM抗原评估了MM反应性调节性T细胞(Tregs)的存在和抑制作用。我们发现MM反应性T细胞在MM患者中很常见,在肿瘤切除后短暂增加,主要针对Melan-A/MART-1,酪氨酸酶,NA17-A和p53。mm特异性Tregs仅在少数患者中检测到,并且在肿瘤切除后早期尤其能抑制mm反应性T细胞。肿瘤特异性自身抗体出现在大多数患者中,但与T细胞反应无关。因此,内源性抗体可能不是mm反应性T细胞的可靠替代参数。
Endogenous tumor-specific T cells are detectable in patients with different tumor types including malignant melanoma (MM). They can control tumor growth, have impact on patient survival and correlate with improved clinical response to immune checkpoint therapy. Thus, they may represent a potent biomarker for respective treatment decisions. So far, major target antigens of endogenous MM-reactive T cells have not been determined systematically. Instead, autoantibodies are discussed as surrogate parameter for MM-specific T cells. Throughout a period of more than 60 days after tumor resection, we therefore determined in 38 non-metastasized primary MM patients and in healthy individuals by IFNγ ELISpot and bead-based fluorescent multiplex assay major target antigens of spontaneous T cell and humoral responses using a broad panel of MM antigens and assessed the presence and suppressive impact of MM-reactive regulatory T cells (Tregs). We show that MM-reactive T cells are frequent in MM patients, transiently increase after tumor removal and are mostly directed against Melan-A/MART-1, Tyrosinase, NA17-A and p53. MM-specific Tregs were only detected in few patients and inhibited MM-reactive T cells particularly early after tumor resection. Tumor-specific autoantibodies occurred in most patients, but did not correlate with T cell responses. Thus, endogenous antibodies may not be reliable surrogate parameters of MM-reactive T cells.
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发表时间: 2014-01
影响因子: 5.8
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将 p53 作为一般肿瘤抗原。
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对免疫治疗有显着反应的患者对酪氨酸酶相关蛋白 (TRP)-2、一种新的 TRP-2 异构体和 NY-ESO-1 黑色素瘤抗原已有免疫力
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