Tumor neoantigens: Building a framework for personalized cancer immunotherapy

Journal of Clinical Investigation

Volumn 125, Issue 9, 2015, Pages 3413-3421

  Gubin, Matthew M ^a,b   Artyomov, Maxim N ^a,b   Mardis, Elaine R ^a,b   Schreiber, Robert D ^a,b  

^a Department of Pathology and Immunology ^*  (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; IMMUNOMODULATING AGENT; TUMOR ANTIGEN; TUMOR NEOANTIGEN; UNCLASSIFIED DRUG;

ANTIGEN FUNCTION; CANCER IMMUNOTHERAPY; CLASSIFICATION; HUMAN; MALIGNANT NEOPLASTIC DISEASE; NEXT GENERATION SEQUENCING; NONHUMAN; PERSONALIZED MEDICINE; PRIORITY JOURNAL; REVIEW; SOMATIC MUTATION; CELLULAR IMMUNITY; DRUG EFFECTS; GENETIC EPIGENESIS; GENETICS; HIGH THROUGHPUT SEQUENCING; IMMUNOLOGY; IMMUNOTHERAPY; MUTATION; NEOPLASMS; PATHOLOGY; PROCEDURES; T LYMPHOCYTE;

ANTIGENS, NEOPLASM; EPIGENESIS, GENETIC; EPITOPES; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; IMMUNITY, CELLULAR; IMMUNOTHERAPY; MUTATION; NEOPLASMS; PRECISION MEDICINE; T-LYMPHOCYTES;

EID: 84941710020     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI80008     Document Type: Review

References (102)

1. Gross L. Intradermal immunization of C3H mice against a sarcoma that originated in an animal of the same line. Cancer Res. 1943;3(5):326-333.
2. Foley EJ. Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Res. 1953;13(12):835-837.
3. Prehn RT, Main JM. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst. 1957;18(6):769-778.
4. Old LJ. Cancer immunology: the search for specificity. Natl Cancer Inst Monogr. 1982;60:193-209.
5. Babbitt BP, Allen PM, Matsueda G, Haber E, Unanue ER. Binding of immunogenic peptides to Ia histocompatibility molecules. Nature. 1985;317(6035):359-361.
6. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987;329(6139):506-512.
7. Cerottini JC, Engers HD, Macdonald HR, Brunner T. Generation of cytotoxic T lymphocytes in vitro. I. Response of normal and immune mouse spleen cells in mixed leukocyte cultures. J Exp Med. 1974;140(3):703-717.
8. Gillis S, Smith KA. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977;268(5616):154-156.
9. De Plaen E, et al. Immunogenic (tum-) variants of mouse tumor P815: cloning of the gene of tum-antigen P91A and identification of the tum-mutation. Proc Natl Acad Sci U S A. 1988;85(7):2274-2278.
10. Monach PA, Meredith SC, Siegel CT, Schreiber H. A unique tumor antigen produced by a single amino acid substitution. Immunity. 1995;2(1):45-59.
11. Dubey P, et al. The immunodominant antigen of an ultraviolet-induced regressor tumor is generated by a somatic point mutation in the DEAD box helicase p68. J Exp Med. 1997;185(4):695-705.
12. Knuth A, Danowski B, Oettgen HF, Old LJ. T-cell-mediated cytotoxicity against autologous malignant melanoma: analysis with interleukin 2-dependent T-cell cultures. Proc Natl Acad Sci U S A. 1984;81(11):3511-3515.
13. Robbins PF, et al. A mutated β-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. J Exp Med. 1996;183(3):1185-1192.
14. van der Bruggen P, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991;254(5038):1643-1647.
15. Coulie PG, Van den Eynde BJ, van der Bruggen P, Boon T. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer. 2014;14(2):135-146.
16. Sahin U, et al. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A. 1995;92(25):11810-11813.
17. Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 2005;5(8):615-625.
18. Vigneron N, Stroobant V, Van den Eynde BJ, van der Bruggen P. Database of T cell-defined human tumor antigens: the 2013 update. Cancer Immun. 2013;13:15.
19. Heemskerk B, Kvistborg P, Schumacher TN. The cancer antigenome. EMBO J. 2013;32(2):194-203.
20. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57-70.
21. Greenman C, et al. Patterns of somatic mutation in human cancer genomes. Nature. 2007;446(7132):153-158.
22. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674.
23. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science. 2013;339(6127):1546-1558.
24. Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69-74.
25. Ohminami H, Yasukawa M, Fujita S. HLA class I-restricted lysis of leukemia cells by a CD8(+) cytotoxic T-lymphocyte clone specific for WT1 peptide. Blood. 2000;95(1):286-293.
26. Kawashima I, Tsai V, Southwood S, Takesako K, Sette A, Celis E. Identification of HLA-A3-restricted cytotoxic T lymphocyte epitopes from carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with peptide-pulsed dendritic cells. Cancer Res. 1999;59(2):431-435.
27. Doyle HA, et al. Isoaspartyl post-Translational modification triggers anti-Tumor T and B lymphocyte immunity. J Biol Chem. 2006;281(43):32676-32683.
28. Cobbold M, et al. MHC class I-associated phosphopeptides are the targets of memorylike immunity in leukemia. Sci Transl Med. 2013;5(203):203ra125.
29. Pardoll D. Does the immune system see tumors as foreign or self? Annu Rev Immunol. 2003;21:807-839.
30. Hogquist KA, Baldwin TA, Jameson SC. Central tolerance: learning self-control in the thymus. Nat Rev Immunol. 2005;5(10):772-782.
31. Stone JD, Harris DT, Kranz DM. TCR affinity for p/MHC formed by tumor antigens that are selfproteins: impact on efficacy and toxicity. Curr Opin Immunol. 2015;33:16-22.
32. Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev. 2002;188:22-32.
33. Lennerz V, et al. The response of autologous T cells to a human melanoma is dominated by mutated neoantigens. Proc Natl Acad Sci U S A. 2005;102(44):16013-16018.
34. Zhou J, Dudley ME, Rosenberg SA, Robbins PF. Persistence of multiple tumor-specific T-cell clones is associated with complete tumor regression in a melanoma patient receiving adoptive cell transfer therapy. J Immunother. 2005;28(1):53-62.
35. Wood LD, et al. The genomic landscapes of human breast and colorectal cancers. Science. 2007;318(5853):1108-1113.
36. Ley TJ, et al. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008;456(7218):66-72.
37. Segal NH, et al. Epitope landscape in breast and colorectal cancer. Cancer Res. 2008;68(3):889-892.
38. Castle JC, et al. Exploiting the mutanome for tumor vaccination. Cancer Res. 2012;72(5):1081-1091.
39. Matsushita H, et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature. 2012;482(7385):400-404.
40. DuPage M, Mazumdar C, Schmidt LM, Cheung AF, Jacks T. Expression of tumour-specific antigens underlies cancer immunoediting. Nature. 2012;482(7385):405-409.
41. Shankaran V, et al. IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001;410(6832):1107-1111.
42. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3(11):991-998.
43. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunitys roles in cancer suppression and promotion. Science. 2011;331(6024):1565-1570.
44. Robbins PF, et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med. 2013;19(6):747-752.
45. van Rooij N, et al. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J Clin Oncol. 2013;31(32):e439-e442.
46. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271(5256):1734-1736.
47. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264.
48. Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2):205-214.
49. Fritsch EF, Rajasagi M, Ott PA, Brusic V, Hacohen N, Wu CJ. HLA-binding properties of tumor neoepitopes in humans. Cancer Immunol Res. 2014;2(6):522-529.
50. Rajasagi M, et al. Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia. Blood. 2014;124(3):453-462.
51. van Buuren MM, Calis JJ, Schumacher TN. High sensitivity of cancer exome-based CD8 T cell neo-antigen identification. Oncoimmunology. 2014;3:e28836.
52. Wick DA, et al. Surveillance of the tumor mutanome by T cells during progression from primary to recurrent ovarian cancer. Clin Cancer Res. 2014;20(5):1125-1134.
53. Mardis ER. Next-generation sequencing platforms. Annu Rev Anal Chem (Palo Alto Calif). 2013;6:287-303.
54. Albert TJ, et al. Direct selection of human genomic loci by microarray hybridization. Nat Methods. 2007;4(11):903-905.
55. Hodges E, et al. Hybrid selection of discrete genomic intervals on custom-designed microarrays for massively parallel sequencing. Nat Protoc. 2009;4(6):960-974.
56. Blumenstiel B, et al. Targeted exon sequencing by in-solution hybrid selection. Curr Protoc Hum Genet. 2010;Chapter 18:Unit 18.4.
57. Cabanski CR, et al. cDNA hybrid capture improves transcriptome analysis on lowinput and archived samples. J Mol Diagn. 2014;16(4):440-451.
58. Blum JS, Wearsch PA, Cresswell P. Pathways of antigen processing. Annu Rev Immunol. 2013;31:443-473.
59. Rock KL, et al. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994;78(5):761-771.
60. Van Kaer L, Ashton-Rickardt PG, Ploegh HL, Tonegawa S. TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4-8+ T cells. Cell. 1992;71(7):1205-1214.
61. Robinson J, Halliwell JA, Hayhurst JD, Flicek P, Parham P, Marsh SG. The IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res. 2015;43(Database issue):D423-D431.
62. Lundegaard C, Lund O, Kesmir C, Brunak S, Nielsen M. Modeling the adaptive immune system: predictions and simulations. Bioinformatics. 2007;23(24):3265-3275.
63. Lin HH, Ray S, Tongchusak S, Reinherz EL, Brusic V. Evaluation of MHC class I peptide binding prediction servers: applications for vaccine research. BMC Immunol. 2008;9:8.
64. Zhang L, Udaka K, Mamitsuka H, Zhu S. Toward more accurate pan-specific MHC-peptide binding prediction: a review of current methods and tools. Brief Bioinform. 2012;13(3):350-364.
65. Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 1999;50(3-4):213-219.
66. Reche PA, Glutting JP, Reinherz EL. Prediction of MHC class I binding peptides using profile motifs. Hum Immunol. 2002;63(9):701-709.
67. Parker KC, Bednarek MA, Coligan JE. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol. 1994;152(1):163-175.
68. Vita R, et al. The immune epitope database (IEDB) 3.0. Nucleic Acids Res. 2015;43(Database issue):D405-D412.
69. Lundegaard C, Lund O, Nielsen M. Prediction of epitopes using neural network based methods. J Immunol Methods. 2011;374(1-2):26-34.
70. Lundegaard C, Lamberth K, Harndahl M, Buus S, Lund O, Nielsen M. NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11. Nucleic Acids Res. 2008;36(Web Server issue):W509-W512.
71. Honeyman MC, Brusic V, Stone NL, Harrison LC. Neural network-based prediction of candidate T-cell epitopes. Nat Biotechnol. 1998;16(10):966-969.
72. Lundegaard C, Nielsen M, Lund O. The validity of predicted T-cell epitopes. Trends Biotechnol. 2006;24(12):537-538.
73. Nielsen M, et al. NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence. PLoS One. 2007;2(8):e796.
74. Hoof I, et al. NetMHCpan, a method for MHC class I binding prediction beyond humans. Immunogenetics. 2009;61(1):1-13.
75. Peters B, Sette A. Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method. BMC Bioinformatics. 2005;6:132.
76. Kim Y, Sidney J, Pinilla C, Sette A, Peters B. Derivation of an amino acid similarity matrix for peptide: MHC binding and its application as a Bayesian prior. BMC Bioinformatics. 2009;10:394.
77. Gubin MM, et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature. 2014;515(7528):577-581.
78. Yadav M, et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature. 2014;515(7528):572-576.
79. Rammensee HG, Singh-Jasuja H. HLA ligandome tumor antigen discovery for personalized vaccine approach. Expert Rev Vaccines. 2013;12(10):1211-1217.
80. Nielsen M, Lundegaard C, Lund O, Kesmir C. The role of the proteasome in generating cytotoxic T-cell epitopes: insights obtained from improved predictions of proteasomal cleavage. Immunogenetics. 2005;57(1-2):33-41.
81. Peters B, Bulik S, Tampe R, Van Endert PM, Holzhutter HG. Identifying MHC class I epitopes by predicting the TAP transport efficiency of epitope precursors. J Immunol. 2003;171(4):1741-1749.
82. Larsen MV, Lundegaard C, Lamberth K, Buus S, Lund O, Nielsen M. Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinformatics. 2007;8:424.
83. Hammer J, Bono E, Gallazzi F, Belunis C, Nagy Z, Sinigaglia F. Precise prediction of major histocompatibility complex class II-peptide interaction based on peptide side chain scanning. J Exp Med. 1994;180(6):2353-2358.
84. Nielsen M, Lund O. NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction. BMC Bioinformatics. 2009;10:296.
85. Nielsen M, Lundegaard C, Lund O. Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method. BMC Bioinformatics. 2007;8:238.
86. Duan F, et al. Genomic and bioinformatic profiling of mutational neoepitopes reveals new rules to predict anticancer immunogenicity. J Exp Med. 2014;211(11):2231-2248.
87. Gnjatic S, et al. Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: correlation with antibody responses. Proc Natl Acad Sci U S A. 2003;100(15):8862-8867.
88. Schumacher T, et al. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature. 2014;512(7514):324-327.
89. Linnemann C, et al. High-Throughput epitope discovery reveals frequent recognition of neoantigens by CD4+ T cells in human melanoma. Nat Med. 2015;21(1):81-85.
90. Kreiter S, et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature. 2015;520(7549):692-696.
91. Tran E, et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014;344(6184):641-645.
92. Carreno BM, et al. A dendritic cell vaccine increases the breadth diversity of melanoma neoantigen-specific T cells. Science. 2015;348(6236):803-808.
93. Snyder A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371(23):2189-2199.
94. Rizvi NA, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124-128.
95. Chowell D, et al. TCR contact residue hydrophobicity is a hallmark of immunogenic CD8+ T cell epitopes. Proc Natl Acad Sci U S A. 2015;112(14):E1754-E1762.
96. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883-899.
97. Trinchieri G. Cancer and inflammation: an old intuition with rapidly evolving new concepts. Annu Rev Immunol. 2012;30:677-706.
98. Hodi FS, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-723.
99. Topalian SL, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-2454.
100. Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348(6230):56-61.
101. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480(7378):480-489.
102. Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1-10.