Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry.
Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry.
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DOI：
10.1038/ncomms13404
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发表时间：
2016-11-21
影响因子：
16.6
通讯作者：
Krackhardt, Angela M.
中科院分区：
文献类型：
--
作者：
Bassani-Sternberg, Michal;Braunlein, Eva;Klar, Richard;Engleitner, Thomas;Sinitcyn, Pavel;Audehm, Stefan;Straub, Melanie;Weber, Julia;Slotta-Huspenina, Julia;Specht, Katja;Martignoni, Marc E.;Werner, Angelika;Hein, Rudiger;Busch, Dirk H.;Peschel, Christian;Rad, Roland;Cox, Jurgen;Mann, Matthias;Krackhardt, Angela M.
虽然突变可能代表免疫治疗的有吸引力的靶点，但从天然肿瘤组织表面上的人白细胞抗原（HLA）分离的突变肽配体的直接鉴定迄今为止还没有成功。使用先进的质谱（MS）分析，我们调查了黑色素瘤相关的免疫肽组，深度为95，500个患者呈递的肽。因此，我们发现了大量有吸引力的靶抗原候选物，包括癌症睾丸抗原和磷酸肽。最重要的是，我们确定肽配体上天然肿瘤组织样本窝藏体细胞突变。11个突变配体中有4个被新抗原特异性T细胞应答证明具有免疫原性。此外，在患者的肿瘤和外周血中检测到对通过MS鉴定的选定新抗原具有特异性的肿瘤反应性T细胞。我们的结论是，通过MS直接鉴定来自原发性肿瘤材料的突变肽配体是可能的，并产生与癌症免疫策略高度相关的真正的新表位。 新抗原决定抗癌免疫反应性并且是免疫治疗的重要功能靶标。在这里，作者使用深度质谱来表征来自人类黑色素瘤组织的新表位，并显示对选定的新抗原具有特异性的肿瘤反应性T细胞的存在。
Although mutations may represent attractive targets for immunotherapy, direct identification of mutated peptide ligands isolated from human leucocyte antigens (HLA) on the surface of native tumour tissue has so far not been successful. Using advanced mass spectrometry (MS) analysis, we survey the melanoma-associated immunopeptidome to a depth of 95,500 patient-presented peptides. We thereby discover a large spectrum of attractive target antigen candidates including cancer testis antigens and phosphopeptides. Most importantly, we identify peptide ligands presented on native tumour tissue samples harbouring somatic mutations. Four of eleven mutated ligands prove to be immunogenic by neoantigen-specific T-cell responses. Moreover, tumour-reactive T cells with specificity for selected neoantigens identified by MS are detected in the patient's tumour and peripheral blood. We conclude that direct identification of mutated peptide ligands from primary tumour material by MS is possible and yields true neoepitopes with high relevance for immunotherapeutic strategies in cancer. Neoantigens determine anti-cancer immunoreactivity and are important functional targets for immunotherapy. Here, the authors use deep mass spectrometry to characterize neoepitopes from human melanoma tissue and show the presence of tumour-reactive T cells with specificity for selected neoantigens.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
82.9
作者：
Gros A;Parkhurst MR;Tran E;Pasetto A;Robbins PF;Ilyas S;Prickett TD;Gartner JJ;Crystal JS;Roberts IM;Trebska-McGowan K;Wunderlich JR;Yang JC;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
15.9
作者：
Cohen, Cyrille J.;Gartner, Jared J.;Robbins, Paul F.
通讯作者：
Robbins, Paul F.
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias