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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,11,19]]},"abstract":"<jats:p>The impact of intratumoral heterogeneity (ITH) and the resultant neoantigen landscape on T cell immunity are poorly understood. ITH is a widely recognized feature of solid tumors and poses distinct challenges related to the development of effective therapeutic strategies, including cancer neoantigen vaccines. Here, we performed deep targeted DNA sequencing of multiple metastases from melanoma patients and observed ubiquitous sharing of clonal and subclonal single nucleotide variants (SNVs) encoding putative HLA class I-restricted neoantigen epitopes. However, spontaneous antitumor CD8+ T cell immunity in peripheral blood and tumors was restricted to a few clonal neoantigens featuring an oligo-\/monoclonal T cell-receptor (TCR) repertoire. Moreover, in various tumors of the 4 patients examined, no neoantigen-specific TCR clonotypes were identified despite clonal neoantigen expression. Mature dendritic cell (mDC) vaccination with tumor-encoded amino acid-substituted (AAS) peptides revealed diverse neoantigen-specific CD8+ T responses, each composed of multiple TCR clonotypes. Isolation of T cell clones by limiting dilution from tumor-infiltrating lymphocytes (TILs) permitted functional validation regarding neoantigen specificity. Gene transfer of TCR\u03b1\u03b2 heterodimers specific for clonal neoantigens confirmed correct TCR clonotype assignments based on high-throughput TCRBV CDR3 sequencing. Our findings implicate immunological ignorance of clonal neoantigens as the basis for ineffective T cell immunity to melanoma and support the concept that therapeutic vaccination, as an adjunct to checkpoint inhibitor treatment, is required to increase the breadth and diversity of neoantigen-specific CD8+ T cells.<\/jats:p>","DOI":"10.1073\/pnas.1906026116","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T20:58:46Z","timestamp":1572901126000},"page":"23662-23670","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["Immunological ignorance is an enabling feature of the oligo-clonal T cell response to melanoma neoantigens"],"prefix":"10.1073","volume":"116","author":[{"given":"Gerald P.","family":"Linette","sequence":"first","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"The Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Becker-Hapak","sequence":"additional","affiliation":[{"name":"McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63110;"},{"name":"Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110;"},{"name":"Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary L.","family":"Skidmore","sequence":"additional","affiliation":[{"name":"McDonnell Genome 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63110;"},{"name":"Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Spencer","sequence":"additional","affiliation":[{"name":"McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63110;"},{"name":"Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110;"},{"name":"Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixuan","family":"Fu","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"The Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"Department of Pathology and Laboratory 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H.","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK 73104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Magrini","sequence":"additional","affiliation":[{"name":"Institute for Genomic Medicine, Nationwide Children\u2019s Hospital, Ohio State University College of Medicine, Columbus, OH 43205;"},{"name":"Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH 43205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Demeter","sequence":"additional","affiliation":[{"name":"McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63110;"},{"name":"Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110;"},{"name":"Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S.","family":"Krupnick","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0843-4271","authenticated-orcid":false,"given":"Obi L.","family":"Griffith","sequence":"additional","affiliation":[{"name":"McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63110;"},{"name":"Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110;"},{"name":"Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malachi","family":"Griffith","sequence":"additional","affiliation":[{"name":"McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63110;"},{"name":"Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110;"},{"name":"Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine R.","family":"Mardis","sequence":"additional","affiliation":[{"name":"Institute for Genomic Medicine, Nationwide Children\u2019s Hospital, Ohio State University College of Medicine, Columbus, OH 43205;"},{"name":"Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH 43205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz M.","family":"Carreno","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"The Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 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Rosenberg, \u2018Final common pathway\u2019 of human cancer immunotherapy: Targeting random somatic mutations. Nat. Immunol. 18, 255\u2013262 (2017).","journal-title":"Nat. Immunol."},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00281-004-0192-0","article-title":"Immunological ignorance of solid tumors","volume":"27","author":"Ochsenbein A. F.","year":"2005","unstructured":"A. F. Ochsenbein, Immunological ignorance of solid tumors. Springer Semin. Immunopathol. 27, 19\u201335 (2005).","journal-title":"Springer Semin. Immunopathol."},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0167-5699(97)01180-8","article-title":"Immunological ignorance of silent antigens as an explanation of tumor evasion","volume":"19","author":"Chen L.","year":"1998","unstructured":"L. Chen, Immunological ignorance of silent antigens as an explanation of tumor evasion. Immunol. Today 19, 27\u201330 (1998).","journal-title":"Immunol. 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Reuben ., TCR repertoire intratumor heterogeneity in localized lung adenocarcinomas: An association with predicted neoantigen heterogeneity and postsurgical recurrence. Cancer Discov. 7, 1088\u20131097 (2017).","journal-title":"Cancer Discov."},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.cell.2017.09.028","article-title":"Tumor and microenvironment evolution during immunotherapy with Nivolumab","volume":"171","author":"Riaz N.","year":"2017","unstructured":"N. Riaz ., (2017) Tumor and microenvironment evolution during immunotherapy with Nivolumab. Cell 171, 934\u2013949.e16.","journal-title":"Cell"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1158\/2326-6066.CIR-16-0001","article-title":"Tumor- and neoantigen-reactive T-cell receptors can be identified based on their frequency in fresh tumor","volume":"4","author":"Pasetto A.","year":"2016","unstructured":"A. Pasetto ., Tumor- and neoantigen-reactive T-cell receptors can be identified based on their frequency in fresh tumor. Cancer Immunol. Res. 4, 734\u2013743 (2016).","journal-title":"Cancer Immunol. Res."},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1126\/science.aaa3828","article-title":"Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells","volume":"348","author":"Carreno B. M.","year":"2015","unstructured":"B. M. Carreno ., Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science 348, 803\u2013808 (2015).","journal-title":"Science"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"15964","DOI":"10.1073\/pnas.1412075111","article-title":"Timing and heterogeneity of mutations associated with drug resistance in metastatic cancers","volume":"111","author":"Bozic I.","year":"2014","unstructured":"I. Bozic, M. A. Nowak, Timing and heterogeneity of mutations associated with drug resistance in metastatic cancers. Proc. Natl. Acad. Sci. U.S.A. 111, 15964\u201315968 (2014).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1158\/2159-8290.CD-15-1020","article-title":"Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy","volume":"5","author":"Sotillo E.","year":"2015","unstructured":"E. Sotillo ., Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 5, 1282\u20131295 (2015).","journal-title":"Cancer Discov."},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"e215","DOI":"10.3324\/haematol.2017.183459","article-title":"Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma","volume":"103","author":"Shalabi H.","year":"2018","unstructured":"H. Shalabi ., Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma. Haematologica 103, e215\u2013e218 (2018).","journal-title":"Haematologica"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"eaaa0984","DOI":"10.1126\/scitranslmed.aaa0984","article-title":"A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma","volume":"9","author":"O\u2019Rourke D. M.","year":"2017","unstructured":"D. M. O\u2019Rourke ., A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci. Transl. Med. 9, eaaa0984 (2017).","journal-title":"Sci. Transl. Med."},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1126\/science.aaf1490","article-title":"Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade","volume":"351","author":"McGranahan N.","year":"2016","unstructured":"N. McGranahan ., Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351, 1463\u20131469 (2016).","journal-title":"Science"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13073-016-0264-5","article-title":"pVAC-Seq: A genome-guided in silico approach to identifying tumor neoantigens","volume":"8","author":"Hundal J.","year":"2016","unstructured":"J. Hundal ., pVAC-Seq: A genome-guided in silico approach to identifying tumor neoantigens. Genome Med. 8, 11 (2016).","journal-title":"Genome Med."},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"e1003665","DOI":"10.1371\/journal.pcbi.1003665","article-title":"SciClone: Inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution","volume":"10","author":"Miller C. A.","year":"2014","unstructured":"C. A. Miller ., SciClone: Inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution. PLoS Comput. Biol. 10, e1003665 (2014).","journal-title":"PLoS Comput. Biol."},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1172\/JCI82416","article-title":"Isolation of neoantigen-specific T cells from tumor and peripheral lymphocytes","volume":"125","author":"Cohen C. J.","year":"2015","unstructured":"C. J. Cohen ., Isolation of neoantigen-specific T cells from tumor and peripheral lymphocytes. J. Clin. Invest. 125, 3981\u20133991 (2015).","journal-title":"J. Clin. Invest."},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.cell.2017.01.018","article-title":"Clonal heterogeneity and tumor evolution: Past, present, and the future","volume":"168","author":"McGranahan N.","year":"2017","unstructured":"N. McGranahan, C. Swanton, Clonal heterogeneity and tumor evolution: Past, present, and the future. Cell 168, 613\u2013628 (2017).","journal-title":"Cell"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1158\/2326-6066.CIR-15-0215","article-title":"Durable complete response from metastatic melanoma after transfer of autologous T cells recognizing 10 mutated tumor antigens","volume":"4","author":"Prickett T. D.","year":"2016","unstructured":"T. D. Prickett ., Durable complete response from metastatic melanoma after transfer of autologous T cells recognizing 10 mutated tumor antigens. Cancer Immunol. Res. 4, 669\u2013678 (2016).","journal-title":"Cancer Immunol. Res."},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1126\/science.aad1253","article-title":"Immunogenicity of somatic mutations in human gastrointestinal cancers","volume":"350","author":"Tran E.","year":"2015","unstructured":"E. Tran ., Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 350, 1387\u20131390 (2015).","journal-title":"Science"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1126\/science.aak9510","article-title":"Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer","volume":"356","author":"Stevanovi\u0107 S.","year":"2017","unstructured":"S. Stevanovi\u0107 ., Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science 356, 200\u2013205 (2017).","journal-title":"Science"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/s41591-018-0040-8","article-title":"Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer","volume":"24","author":"Zacharakis N.","year":"2018","unstructured":"N. Zacharakis ., Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat. Med. 24, 724\u2013730 (2018).","journal-title":"Nat. Med."},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41591-018-0266-5","article-title":"Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers","volume":"25","author":"Scheper W.","year":"2019","unstructured":"W. Scheper ., Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers. Nat. Med. 25, 89\u201394 (2019).","journal-title":"Nat. Med."},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1158\/2159-8290.CD-17-1418","article-title":"Combined analysis of antigen presentation and T-cell recognition reveals restricted immune responses in melanoma","volume":"8","author":"Kalaora S.","year":"2018","unstructured":"S. Kalaora ., Combined analysis of antigen presentation and T-cell recognition reveals restricted immune responses in melanoma. Cancer Discov. 8, 1366\u20131375 (2018).","journal-title":"Cancer Discov."},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/nature14001","article-title":"Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing","volume":"515","author":"Yadav M.","year":"2014","unstructured":"M. Yadav ., Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature 515, 572\u2013576 (2014).","journal-title":"Nature"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nature13988","article-title":"Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens","volume":"515","author":"Gubin M. M.","year":"2014","unstructured":"M. M. Gubin ., Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 515, 577\u2013581 (2014).","journal-title":"Nature"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1158\/2159-8290.CD-17-1417","article-title":"Antitumor activity associated with prolonged persistence of adoptively transferred NY-ESO-1 c259T cells in synovial sarcoma","volume":"8","author":"D\u2019Angelo S. P.","year":"2018","unstructured":"S. P. D\u2019Angelo ., Antitumor activity associated with prolonged persistence of adoptively transferred NY-ESO-1 c259T cells in synovial sarcoma. Cancer Discov. 8, 944\u2013957 (2018).","journal-title":"Cancer Discov."},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1073\/pnas.96.5.2233","article-title":"Immune surveillance against a solid tumor fails because of immunological ignorance","volume":"96","author":"Ochsenbein A. F.","year":"1999","unstructured":"A. F. Ochsenbein ., Immune surveillance against a solid tumor fails because of immunological ignorance. Proc. Natl. Acad. Sci. U.S.A. 96, 2233\u20132238 (1999).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1038\/35082583","article-title":"Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction","volume":"411","author":"Ochsenbein A. F.","year":"2001","unstructured":"A. F. Ochsenbein ., Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction. Nature 411, 1058\u20131064 (2001).","journal-title":"Nature"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S1074-7613(02)00480-6","article-title":"Increasing tumor antigen expression overcomes \u201cignorance\u201d to solid tumors via crosspresentation by bone marrow-derived stromal cells","volume":"17","author":"Spiotto M. T.","year":"2002","unstructured":"M. T. Spiotto ., Increasing tumor antigen expression overcomes \u201cignorance\u201d to solid tumors via crosspresentation by bone marrow-derived stromal cells. Immunity 17, 737\u2013747 (2002).","journal-title":"Immunity"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nature21349","article-title":"Elements of cancer immunity and the cancer-immune set point","volume":"541","author":"Chen D. S.","year":"2017","unstructured":"D. S. Chen, I. Mellman, Elements of cancer immunity and the cancer-immune set point. Nature 541, 321\u2013330 (2017).","journal-title":"Nature"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature22991","article-title":"An immunogenic personal neoantigen vaccine for patients with melanoma","volume":"547","author":"Ott P. A.","year":"2017","unstructured":"P. A. Ott ., An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547, 217\u2013221 (2017).","journal-title":"Nature"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nature23003","article-title":"Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer","volume":"547","author":"Sahin U.","year":"2017","unstructured":"U. Sahin ., Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547, 222\u2013226 (2017).","journal-title":"Nature"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41586-018-0792-9","article-title":"Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial","volume":"565","author":"Keskin D. B.","year":"2019","unstructured":"D. B. Keskin ., Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 565, 234\u2013239 (2019).","journal-title":"Nature"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/s41586-018-0810-y","article-title":"Actively personalized vaccination trial for newly diagnosed glioblastoma","volume":"565","author":"Hilf N.","year":"2019","unstructured":"N. Hilf ., Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature 565, 240\u2013245 (2019).","journal-title":"Nature"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"eaao5931","DOI":"10.1126\/scitranslmed.aao5931","article-title":"Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer","volume":"10","author":"Tanyi J. L.","year":"2018","unstructured":"J. L. Tanyi ., Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Sci. Transl. Med. 10, eaao5931 (2018).","journal-title":"Sci. Transl. Med."},{"key":"e_1_3_4_38_2","unstructured":"M. Griffith . Search for MEL66 and MEL69 data. dbGaP Genotypes and Phenotypes database. https:\/\/www.ncbi.nlm.nih.gov\/projects\/gap\/cgi-bin\/study.cgi?study_id=phs001005.v2.p1. Deposited 22 October 2019."},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.1172\/JCI68395","article-title":"IL-12p70-producing patient DC vaccine elicits Tc1-polarized immunity","volume":"123","author":"Carreno B. M.","year":"2013","unstructured":"B. M. Carreno ., IL-12p70-producing patient DC vaccine elicits Tc1-polarized immunity. J. Clin. Invest. 123, 3383\u20133394 (2013).","journal-title":"J. Clin. Invest."},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nmeth.3364","article-title":"MiXCR: Software for comprehensive adaptive immunity profiling","volume":"12","author":"Bolotin D. A.","year":"2015","unstructured":"D. A. Bolotin ., MiXCR: Software for comprehensive adaptive immunity profiling. Nat. Methods 12, 380\u2013381 (2015).","journal-title":"Nat. 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