Sensitive and frequent identification of high avidity neo-epitope specific CD8 (+) T cells in immunotherapy-naive ovarian cancer.
Sensitive and frequent identification of high avidity neo-epitope specific CD8 (+) T cells in immunotherapy-naive ovarian cancer.
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DOI：
10.1038/s41467-018-03301-0
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发表时间：
2018-03-15
影响因子：
16.6
通讯作者：
Harari A
中科院分区：
文献类型：
--
作者：
Bobisse S;Genolet R;Roberti A;Tanyi JL;Racle J;Stevenson BJ;Iseli C;Michel A;Le Bitoux MA;Guillaume P;Schmidt J;Bianchi V;Dangaj D;Fenwick C;Derré L;Xenarios I;Michielin O;Romero P;Monos DS;Zoete V;Gfeller D;Kandalaft LE;Coukos G;Harari A
针对来自非同义体细胞突变的私有肿瘤新抗原的免疫治疗是个体化癌症免疫治疗的一种有前途的策略。然而，在低突变负荷肿瘤类型中的可行性仍然未知。对循环和肿瘤浸润淋巴细胞（TIL）的新表位特异性CD8+ T细胞进行全面和深入的分析，可以迅速鉴定出来自大多数未接受免疫治疗的晚期上皮性卵巢癌患者的寡克隆和多功能细胞。新表位识别在循环T细胞和TIL之间是不一致的，并且更可能在TIL中发现，其显示出比其血液对应物更高的功能亲合力和具有更高预测亲和力的独特TCR。我们的研究结果表明，即使在具有相对低数量的体细胞突变的肿瘤中，也可以实现新表位特异性CD8+ T细胞的鉴定，并且TIL中的新表位验证为基于突变组的个性化免疫疗法扩展了对此类肿瘤的机会。上皮性卵巢癌（EOC）具有低突变负荷。在这里，作者分析了19例EOC患者的循环和肿瘤浸润淋巴细胞（TIL），并报告了新抗原反应性T细胞从两个区室中频繁恢复，但具有不同的TCR库，在TIL中具有更高的亲和力。
Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8+ T cells has allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naive patients with advanced epithelial ovarian cancer studied. Neo-epitope recognition is discordant between circulating T cells and TILs, and is more likely to be found among TILs, which display higher functional avidity and unique TCRs with higher predicted affinity than their blood counterparts. Our results imply that identification of neo-epitope specific CD8+ T cells is achievable even in tumors with relatively low number of somatic mutations, and neo-epitope validation in TILs extends opportunities for mutanome-based personalized immunotherapies to such tumors. Epithelial ovarian cancer (EOC) has low mutational load. Here the authors analyze circulating and tumor-infiltrating lymphocytes (TILs) from 19 EOC patients and report frequent recovery of neo-antigen-reactive T cells from both compartments but with distinct TCR repertoires that have higher affinity in TILs.
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影响因子：
82.9
作者：
Harari A;Rozot V;Bellutti Enders F;Perreau M;Stalder JM;Nicod LP;Cavassini M;Calandra T;Blanchet CL;Jaton K;Faouzi M;Day CL;Hanekom WA;Bart PA;Pantaleo G
通讯作者：
Pantaleo G
影响因子：
15.3
作者：
Harari, Alexandre;Bart, Pierre-Alexandre;Stoehr, Wolfgang;Tapia, Gonzalo;Garcia, Miguel;Medjitna-Rais, Emmanuelle;Burnet, Severine;Cellerai, Cristina;Erlwein, Otto;Barber, Tristan;Moog, Christiane;Liljestrom, Peter;Wagner, Ralf;Wolf, Hans;Kraehenbuhl, Jean-Pierre;Esteban, Mariano;Heeney, Jonathan;Frachette, Marie-Joelle;Tartaglia, James;McCormack, Sheena;Babiker, Abdel;Weber, Jonathan;Pantaleo, Giuseppe
通讯作者：
Pantaleo, Giuseppe
DOI：
10.1056/nejmoa1407222
发表时间：
2014-10-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Maude SL;Frey N;Shaw PA;Aplenc R;Barrett DM;Bunin NJ;Chew A;Gonzalez VE;Zheng Z;Lacey SF;Mahnke YD;Melenhorst JJ;Rheingold SR;Shen A;Teachey DT;Levine BL;June CH;Porter DL;Grupp SA
通讯作者：
Grupp SA
影响因子：
3
作者：
Lee, MS;Feig, M;Brooks, CL
通讯作者：
Brooks, CL
影响因子：
3.7
作者：
Leimgruber A;Ferber M;Irving M;Hussain-Kahn H;Wieckowski S;Derré L;Rufer N;Zoete V;Michielin O
通讯作者：
Michielin O