Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival.
Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival.
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DOI：
10.1101/gr.165985.113
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发表时间：
2014-05
期刊：
影响因子：
7
通讯作者：
Holt RA
中科院分区：
文献类型：
--
作者：
Brown SD;Warren RL;Gibb EA;Martin SD;Spinelli JJ;Nelson BH;Holt RA
体细胞错义突变可以启动肿瘤的发生，反过来，也可以启动抗肿瘤细胞毒性T细胞(CTL)反应。肿瘤基因组分析揭示了肿瘤错义突变图谱的极端异质性，但它们与肿瘤免疫学和患者预后的相关性仍有待全面评估。在这里，对于来自六个肿瘤部位的515名患者，我们使用来自癌症基因组图谱的RNA-Seq数据来识别被预测为免疫原性的突变，因为它们产生了由每个患者的自体HLA-A等位基因编码的MHC蛋白呈现的突变表位。突变表位与患者存活率的增加有关。此外，从CD8A基因的表达推断，相应的肿瘤具有更高的CTL含量，并且CTL耗竭标记PDCD1和CTLA4的表达增加。在没有CTL浸润证据的肿瘤中，突变表位非常稀少。这些发现表明，预测的免疫原性突变的丰富性可能有助于识别可能受益于检查点封锁和相关免疫疗法的患者。
Somatic missense mutations can initiate tumorogenesis and, conversely, anti-tumor cytotoxic T cell (CTL) responses. Tumor genome analysis has revealed extreme heterogeneity among tumor missense mutation profiles, but their relevance to tumor immunology and patient outcomes has awaited comprehensive evaluation. Here, for 515 patients from six tumor sites, we used RNA-seq data from The Cancer Genome Atlas to identify mutations that are predicted to be immunogenic in that they yielded mutational epitopes presented by the MHC proteins encoded by each patient’s autologous HLA-A alleles. Mutational epitopes were associated with increased patient survival. Moreover, the corresponding tumors had higher CTL content, inferred from CD8A gene expression, and elevated expression of the CTL exhaustion markers PDCD1 and CTLA4. Mutational epitopes were very scarce in tumors without evidence of CTL infiltration. These findings suggest that the abundance of predicted immunogenic mutations may be useful for identifying patients likely to benefit from checkpoint blockade and related immunotherapies.
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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：
64.8
作者：
Chin, L.;Meyerson, M.;Aldape, K.;Bigner, D.;Mikkelsen, T.;VandenBerg, S.;Kahn, A.;Penny, R.;Ferguson, M. L.;Gerhard, D. S.;Getz, G.;Brennan, C.;Taylor, B. S.;Winckler, W.;Park, P.;Ladanyi, M.;Hoadley, K. A.;Verhaak, R. G. W.;Hayes, D. N.;Spellman, Paul T.;Absher, D.;Weir, B. A.;Ding, L.;Wheeler, D.;Lawrence, M. S.;Cibulskis, K.;Mardis, E.;Zhang, Jinghui;Wilson, R. K.;Donehower, L.;Wheeler, D. A.;Purdom, E.;Wallis, J.;Laird, P. W.;Herman, J. G.;Schuebel, K. E.;Weisenberger, D. J.;Baylin, S. B.;Schultz, N.;Yao, Jun;Wiedemeyer, R.;Weinstein, J.;Sander, C.;Gibbs, R. A.;Gray, J.;Kucherlapati, R.;Lander, E. S.;Myers, R. M.;Perou, C. M.;McLendon, Roger;Friedman, Allan;Van Meir, Erwin G;Brat, Daniel J;Mastrogianakis, Gena Marie;Olson, Jeffrey J;Lehman, Norman;Yung, W. K. Alfred;Bogler, Oliver;Berger, Mitchel;Prados, Michael;Muzny, Donna;Morgan, Margaret;Scherer, Steve;Sabo, Aniko;Nazareth, Lynn;Lewis, Lora;Hall, Otis;Zhu, Yiming;Ren, Yanru;Alvi, Omar;Yao, Jiqiang;Hawes, Alicia;Jhangiani, Shalini;Fowler, Gerald;San Lucas, Anthony;Kovar, Christie;Cree, Andrew;Dinh, Huyen;Santibanez, Jireh;Joshi, Vandita;Gonzalez-Garay, Manuel L.;Miller, Christopher A.;Milosavljevic, Aleksandar;Sougnez, Carrie;Fennell, Tim;Mahan, Scott;Wilkinson, Jane;Ziaugra, Liuda;Onofrio, Robert;Bloom, Toby;Nicol, Rob;Ardlie, Kristin;Baldwin, Jennifer;Gabriel, Stacey;Fulton, Robert S.;McLellan, Michael D.;Larson, David E.;Shi, Xiaoqi;Abbott, Rachel;Fulton, Lucinda;Chen, Ken;Koboldt, Daniel C.;Wendl, Michael C.;Meyer, Rick;Tang, Yuzhu;Lin, Ling;Osborne, John R.;Dunford-Shore, Brian H.;Miner, Tracie L.;Delehaunty, Kim;Markovic, Chris;Swift, Gary;Courtney, William;Pohl, Craig;Abbott, Scott;Hawkins, Amy;Leong, Shin;Haipek, Carrie;Schmidt, Heather;Wiechert, Maddy;Vickery, Tammi;Scott, Sacha;Dooling, David J.;Chinwalla, Asif;Weinstock, George M.;O'Kelly, Michael;Robinson, Jim;Alexe, Gabriele;Beroukhim, Rameen;Carter, Scott;Chiang, Derek;Gould, Josh;Gupta, Supriya;Korn, Josh;Mermel, Craig;Mesirov, Jill;Monti, Stefano;Nguyen, Huy;Parkin, Melissa;Reich, Michael;Stransky, Nicolas;Garraway, Levi;Golub, Todd;Protopopov, Alexei;Perna, Ilana;Aronson, Sandy;Sathiamoorthy, Narayan;Ren, Georgia;Kim, Hyunsoo;Kong, Sek Won;Xiao, Yonghong;Kohane, Isaac S.;Seidman, Jon;Cope, Leslie;Pan, Fei;Van Den Berg, David;Van Neste, Leander;Yi, Joo Mi;Li, Jun Z.;Southwick, Audrey;Brady, Shannon;Aggarwal, Amita;Chung, Tisha;Sherlock, Gavin;Brooks, James D.;Jakkula, Lakshmi R.;Lapuk, Anna V.;Marr, Henry;Dorton, Shannon;Choi, Yoon Gi;Han, Ju;Ray, Amrita;Wang, Victoria;Durinck, Steffen;Robinson, Mark;Wang, Nicholas J.;Vranizan, Karen;Peng, Vivian;Van Name, Eric;Fontenay, Gerald V.;Ngai, John;Conboy, John G.;Parvin, Bahram;Feiler, Heidi S.;Speed, Terence P.;Socci, Nicholas D.;Olshen, Adam;Lash, Alex;Reva, Boris;Antipin, Yevgeniy;Stukalov, Alexey;Gross, Benjamin;Cerami, Ethan;Wang, Wei Qing;Qin, Li-Xuan;Seshan, Venkatraman E.;Villafania, Liliana;Cavatore, Magali;Borsu, Laetitia;Viale, Agnes;Gerald, William;Topal, Michael D.;Qi, Yuan;Balu, Sai;Shi, Yan;Wu, George;Bittner, Michael;Shelton, Troy;Lenkiewicz, Elizabeth;Morris, Scott;Beasley, Debbie;Sanders, Sheri;Sfeir, Robert;Chen, Jessica;Nassau, David;Feng, Larry;Hickey, Erin;Schaefer, Carl;Madhavan, Subha;Buetow, Ken;Barker, Anna;Vockley, Joseph;Compton, Carolyn;Vaught, Jim;Fielding, Peter;Collins, Francis;Good, Peter;Guyer, Mark;Ozenberger, Brad;Peterson, Jane;Thomson, Elizabeth
通讯作者：
Thomson, Elizabeth
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM
影响因子：
11.2
作者：
Castle, John C.;Kreiter, Sebastian;Sahin, Ugur
通讯作者：
Sahin, Ugur
影响因子：
64.8
作者：
Bell, D.;Berchuck, A.;Birrer, M.;Chien, J.;Cramer, D. W.;Dao, F.;Dhir, R.;DiSaia, P.;Gabra, H.;Glenn, P.;Godwin, A. K.;Gross, J.;Hartmann, L.;Huang, M.;Huntsman, D. G.;Iacocca, M.;Imielinski, M.;Kalloger, S.;Karlan, B. Y.;Levine, D. A.;Mills, G. B.;Morrison, C.;Mutch, D.;Olvera, N.;Orsulic, S.;Park, K.;Petrelli, N.;Rabeno, B.;Rader, J. S.;Sikic, B. I.;Smith-McCune, K.;Sood, A. K.;Bowtell, D.;Penny, R.;Testa, J. R.;Chang, K.;Dinh, H. H.;Drummond, J. A.;Fowler, G.;Gunaratne, P.;Hawes, A. C.;Kovar, C. L.;Lewis, L. R.;Morgan, M. B.;Newsham, I. F.;Santibanez, J.;Reid, J. G.;Trevino, L. R.;Wu, Y. -Q.;Wang, M.;Muzny, D. M.;Wheeler, D. A.;Gibbs, R. A.;Getz, G.;Lawrence, M. S.;Cibulskis, K.;Sivachenko, A. Y.;Sougnez, C.;Voet, D.;Wilkinson, J.;Bloom, T.;Ardlie, K.;Fennell, T.;Baldwin, J.;Gabriel, S.;Lander, E. S.;Ding, L.;Fulton, R. S.;Koboldt, D. C.;McLellan, M. D.;Wylie, T.;Walker, J.;O'Laughlin, M.;Dooling, D. J.;Fulton, L.;Abbott, R.;Dees, N. D.;Zhang, Q.;Kandoth, C.;Wendl, M.;Schierding, W.;Shen, D.;Harris, C. C.;Schmidt, H.;Kalicki, J.;Delehaunty, K. D.;Fronick, C. C.;Demeter, R.;Cook, L.;Wallis, J. W.;Lin, L.;Magrini, V. J.;Hodges, J. S.;Eldred, J. M.;Smith, S. M.;Pohl, C. S.;Vandin, F.;Raphael, B. J.;Weinstock, G. M.;Mardis, R.;Wilson, R. K.;Meyerson, M.;Winckler, W.;Getz, G.;Verhaak, R. G. W.;Carter, S. L.;Mermel, C. H.;Saksena, G.;Nguyen, H.;Onofrio, R. C.;Lawrence, M. S.;Hubbard, D.;Gupta, S.;Crenshaw, A.;Ramos, A. H.;Ardlie, K.;Chin, L.;Protopopov, A.;Zhang, Juinhua;Kim, T. M.;Perna, I.;Xiao, Y.;Zhang, H.;Ren, G.;Sathiamoorthy, N.;Park, R. W.;Lee, E.;Park, P. J.;Kucherlapati, R.;Absher, D. M.;Waite, L.;Sherlock, G.;Brooks, J. D.;Li, J. Z.;Xu, J.;Myers, R. M.;Laird, P. W.;Cope, L.;Herman, J. G.;Shen, H.;Weisenberger, D. J.;Noushmehr, H.;Pan, F.;Triche, T., Jr.;Berman, B. P.;Van den Berg, D. J.;Buckley, J.;Baylin, S. B.;Spellman, P. T.;Purdom, E.;Neuvial, P.;Bengtsson, H.;Jakkula, L. R.;Durinck, S.;Han, J.;Dorton, S.;Marr, H.;Choi, Y. G.;Wang, V.;Wang, N. J.;Ngai, J.;Conboy, J. G.;Parvin, B.;Feiler, H. S.;Speed, T. P.;Gray, J. W.;Levine, D. A.;Socci, N. D.;Liang, Y.;Taylor, B. S.;Schultz, N.;Borsu, L.;Lash, A. E.;Brennan, C.;Viale, A.;Sander, C.;Ladanyi, M.;Hoadley, K. A.;Meng, S.;Du, Y.;Shi, Y.;Li, L.;Turman, Y. J.;Zang, D.;Helms, E. B.;Balu, S.;Zhou, X.;Wu, J.;Topal, M. D.;Hayes, D. N.;Perou, C. M.;Getz, G.;Voet, D.;Saksena, G.;Zhang, Junihua;Zhang, H.;Wu, C. J.;Shukla, S.;Cibulskis, K.;Lawrence, M. S.;Sivachenko, A.;Jing, R.;Park, R. W.;Liu, Y.;Park, P. J.;Noble, M.;Chin, L.;Carter, H.;Kim, D.;Karchin, R.;Spellman, P. T.;Purdom, E.;Neuvial, P.;Bengtsson, H.;Durinck, S.;Han, J.;Korkola, J. E.;Heiser, L. M.;Cho, R. J.;Hu, Z.;Parvin, B.;Speed, T. P.;Gray, J. W.;Schultz, N.;Cerami, E.;Taylor, B. S.;Olshen, A.;Reva, B.;Antipin, Y.;Shen, R.;Mankoo, P.;Sheridan, R.;Ciriello, G.;Chang, W. K.;Bernanke, J. A.;Borsu, L.;Levine, D. A.;Ladanyi, M.;Sander, C.;Haussler, D.;Benz, C. C.;Stuart, J. M.;Benz, S. C.;Sanborn, J. Z.;Vaske, C. J.;Zhu, J.;Szeto, C.;Scott, G. K.;Yau, C.;Hoadley, K. A.;Du, Y.;Balu, S.;Hayes, D. N.;Perou, C. M.;Wilkerson, M. D.;Zhang, N.;Akbani, R.;Baggerly, K. A.;Yung, W. K.;Mills, G. B.;Weinstein, J. N.;Penny, R.;Shelton, T.;Grimm, D.;Hatfield, M.;Morris, S.;Yena, P.;Rhodes, P.;Sherman, M.;Paulauskis, J.;Millis, S.;Kahn, A.;Greene, J. M.;Sfeir, R.;Jensen, M. A.;Chen, J.;Whitmore, J.;Alonso, S.;Jordan, J.;Chu, A.;Zhang, Jinghui;Barker, A.;Compton, C.;Eley, G.;Ferguson, M.;Fielding, P.;Gerhard, D. S.;Myles, R.;Schaefer, C.;Shaw, K. R. Mills;Vaught, J.;Vockley, J. B.;Good, P. J.;Guyer, M. S.;Ozenberger, B.;Peterson, J.;Thomson, E.
通讯作者：
Thomson, E.