Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells.
Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells.
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癌症免疫疗法。树突状细胞疫苗增加了黑色素瘤新抗原特异性T细胞的广度和多样性。
DOI：
10.1126/science.aaa3828
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发表时间：
2015-05-15
期刊：
影响因子：
--
通讯作者：
Linette GP
中科院分区：
文献类型：
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作者：
Carreno BM;Magrini V;Becker-Hapak M;Kaabinejadian S;Hundal J;Petti AA;Ly A;Lie WR;Hildebrand WH;Mardis ER;Linette GP
针对肿瘤编码的氨基酸取代（AAS）的T细胞免疫发生在一些黑素瘤患者中。这暗示错义突变（MM）是患者特异性新抗原的来源。然而，缺乏对这些推定的新抗原作为抗肿瘤免疫的经验证的靶标的系统评价。此外，疫苗接种是否能增强这种反应尚不清楚。在这里，我们表明，树突状细胞疫苗增加自然发生的，并揭示了新的HLA I类限制性新抗原在晚期黑色素瘤患者。通过质谱法证实了人黑素瘤中HLA-A*02：01对新抗原的呈递。在TCRVβ使用和克隆组成方面，疫苗接种促进了多样化的新抗原特异性T细胞受体库。我们的研究结果表明，针对肿瘤AAS的疫苗接种拓宽了抗肿瘤免疫的抗原宽度和克隆多样性。
T cell immunity directed against tumor-encoded amino acid substitutions (AAS) occurs in some melanoma patients. This implicates missense mutations (MM) as a source of patient-specific neoantigens. However, a systematic evaluation of these putative neoantigens as validated targets of anti-tumor immunity is lacking. Moreover, whether vaccination can augment such responses is unknown. Here we show that a dendritic cell vaccine increased naturally occurring and revealed new HLA class I-restricted neoantigens in patients with advanced melanoma. The presentation of neoantigens by HLA-A*02:01 in human melanoma was confirmed by mass spectrometry. Vaccination promoted a diverse neoantigen-specific T cell receptor repertoire in terms of both TCRVβ usage and clonal composition. Our results demonstrate that vaccination directed at tumor AAS broadens the antigenic breadth and clonal diversity of anti-tumor immunity.