Finding neoepitopes in mouse models of personalized cancer immunotherapy
Received date: 25 Apr 2016
Accepted date: 15 Aug 2016
Published date: 04 Nov 2016
Copyright
BACKGROUND: Cancer immunotherapy uses one’s own immune system to fight cancerous cells. As immune system is hard-wired to distinguish self and non-self, cancer immunotherapy is predicted to target cancerous cells specifically, therefore is less toxic than chemotherapy and radiation therapy, two major treatments for cancer. Cancer immunologists have spent decades to search for the specific targets in cancerous cells.
METHODS: Due to the recent advances in high throughput sequencing and bioinformatics, evidence has merged that the neoantigens in cancerous cells are probably the cancer-specific targets that lead to the destruction of cancer. We will review the transplantable murine tumor models for cancer immunotherapy and the bioinformatics tools used to navigate mouse genome to identify tumor-rejecting neoantigens.
RESULTS: Several groups have independently identified point mutations that can be recognized by T cells of host immune system. It is consistent with the note that the formation of peptide-MHC I-TCR complex is critical to activate T cells. Both anchor residue and TCR-facing residue mutations have been reported. While TCR-facing residue mutations may directly activate specific T cells, anchor residue mutations improve the binding of peptides to MHC I molecules, which increases the presentation of peptides and the T cell activation indirectly.
CONCLUSIONS: Our work indicates that the affinity of neoepitopes for MHC I is not a predictor for anti-tumor immune responses in mice. Instead differential agretopic index (DAI), the numerical difference of epitope-MHC I affinities between the mutated and un-mutated sequences is a significant predictor. A similar bioinformatics pipeline has been developed to generate personalized vaccines to treat human ovarian cancer in a Phase I clinical trial.
Sahar Al Seesi , Alok Das Mohapatra , Arpita Pawashe , Ion I. Mandoiu , Fei Duan . Finding neoepitopes in mouse models of personalized cancer immunotherapy[J]. Frontiers in Biology, 2016 , 11(5) : 366 -375 . DOI: 10.1007/s11515-016-1422-2
1 |
Al Seesi S, Tiagueu Y T, Zelikovsky A, Măndoiu I I (2014). Bootstrap-based differential gene expression analysis for RNA-Seq data with and without replicates. BMC Genomics, 15(8 Suppl 8): S2
|
2 |
Basombrio M A (1970).Search for common antigenicities among twenty-five sarcomas induced by methylcholanthrene. Cancer Res, 30(10): 2458–262
|
3 |
Bentley D R, Balasubramanian S, Swerdlow H P, Smith G P, Milton J, Brown C G, Hall K P, Evers D J, Barnes C L, Bignell H R, Boutell J M, Bryant J, Carter R J, Keira Cheetham R, Cox A J, Ellis D J, Flatbush M R, Gormley N A, Humphray S J, Irving L J, Karbelashvili M S, Kirk S M, Li H, Liu X, Maisinger K S, Murray L J, Obradovic B, Ost T, Parkinson M L, Pratt M R, Rasolonjatovo I M, Reed M T, Rigatti R, Rodighiero C, Ross M T, Sabot A, Sankar S V, Scally A, Schroth G P, Smith M E, Smith V P, Spiridou A, Torrance P E, Tzonev S S, Vermaas E H, Walter K, Wu X, Zhang L, Alam M D, Anastasi C, Aniebo I C, Bailey D M, Bancarz I R, Banerjee S, Barbour S G, Baybayan P A, Benoit V A, Benson K F, Bevis C, Black P J, Boodhun A, Brennan J S, Bridgham J A, Brown R C, Brown A A, Buermann D H, Bundu A A, Burrows J C, Carter N P, Castillo N, Chiara E, Catenazzi MChang S, Neil Cooley R, Crake N R, Dada O O, Diakoumakos K D, Dominguez-Fernandez B, Earnshaw D J, Egbujor U C, Elmore D W, Etchin S S, Ewan M R, Fedurco M, Fraser L J, Fuentes Fajardo K V, Scott Furey W, George D, Gietzen K J, Goddard C P, Golda G S, Granieri P A, Green D E, Gustafson D L, Hansen N F, Harnish K, Haudenschild C D, Heyer N I, Hims M M, Ho J T, Horgan A M, Hoschler K, Hurwitz S, Ivanov D V, Johnson M Q, James T, Huw Jones T A, Kang G D, Kerelska T H, Kersey A D, Khrebtukova I, Kindwall A P, Kingsbury Z, Kokko-Gonzales P I, Kumar A, Laurent M A, Lawley C T, Lee S E, Lee X, Liao A K, Loch J A, Lok M, Luo S, Mammen R M, Martin J W, McCauley P G, McNitt P, Mehta P, Moon K W, Mullens J W, Newington T, Ning Z, Ling Ng B, Novo S M, O’Neill M J, Osborne M A, Osnowski A, Ostadan O, Paraschos L L, Pickering L, Pike A C, Pike A C, Chris Pinkard D, Pliskin D P, Podhasky J, Quijano V J, Raczy C, Rae V H, Rawlings S R, Chiva Rodriguez A, Roe P M, Rogers J, Rogert Bacigalupo M C, Romanov N, Romieu A, Roth R K, Rourke N J, Ruediger S T, Rusman E, Sanches-Kuiper R M, Schenker M R, Seoane J M, Shaw R J, Shiver M K, Short S W, Sizto N L, Sluis J P, Smith M A, Ernest Sohna Sohna J, Spence E J, Stevens K, Sutton N, Szajkowski L, Tregidgo C L, Turcatti G, Vandevondele S, Verhovsky Y, Virk S M, Wakelin S, Walcott G C, Wang J, Worsley G J, Yan J, Yau L, Zuerlein M, Rogers J, Mullikin J C, Hurles M E, McCooke N J, West J S, Oaks F L, Lundberg P L, Klenerman D, Durbin R, Smith A J (2008). Accurate whole human genome sequencing using reversible terminator chemistry. Nature, 456(7218): 53–59
|
4 |
Berman J N, Chiu P P L, Dellaire G (2014). Preclinical animal models for cancer genomics..In: Dellair G, Berman J N, Arceci R J, eds Cancer Genomics: from Bench to Personalized Medicine, Elsevier Inc., 110–126
|
5 |
Bielas J H, Loeb K R, Rubin B P, True L D, Loeb L A (2006). From the Cover: Human cancers express a mutator phenotype. Proc Natl Acad Sci USA, 103(48):18238–18242
|
6 |
Blanchard T, Srivastava P K, Duan F (2013). Vaccines against advanced melanoma. Clin Dermatol, 31(2): 179–190
|
7 |
Boland J F, Chung C C, Roberson D, Mitchell J, Zhang X, Im K M, He J, Chanock S J, Yeager M, Dean M (2013). The new sequencer on the block: comparison of Life Technology’s Proton sequencer to an Illumina HiSeq for whole-exome sequencing. Hum Genet, 132(10): 1153–1163
|
8 |
Bolger A M, Lohse M, Usadel B (2014). Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics, 30(15): 2114–2120
|
9 |
Boon T, van der Bruggen P (1996). Human tumor antigens recognized by T lymphocytes. J Exp Med, 183(3): 725–729
|
10 |
Castle J C, Kreiter S, Diekmann J, Löwer M, van de Roemer N, de Graaf J, Selmi A, Diken M, Boegel S, Paret C, Koslowski M, Kuhn A N, Britten C M, Huber C, Türeci O, Sahin U (2012). Exploiting the mutanome for tumor vaccination. Cancer Res, 72(5): 1081–1091
|
11 |
Cheon D J, Orsulic S (2011). Mouse models of cancer. Annu Rev Pathol, 6(1): 95–119
|
12 |
Dranoff G (2012). Experimental mouse tumour models: what can be learnt about human cancer immunology? Nat Rev Immunol, 12(1): 61–66
|
13 |
Duan F, Duitama J, Al Seesi S, Ayres C M, Corcelli S A, Pawashe A P, Blanchard T, McMahon D, Sidney J, Sette A, Baker B M, Mandoiu I I, Srivastava P K (2014). Genomic and bioinformatic profiling of mutational neoepitopes reveals new rules to predict anticancer immunogenicity. J Exp Med, 211(11): 2231–2248
|
14 |
Duan F, Lin Y, Liu C, Engelhorn M E, Cohen A D, Curran M, Sakaguchi S, Merghoub T, Terzulli S, Wolchok J D, Houghton A N (2009). Immune rejection of mouse tumors expressing mutated self. Cancer Res, 69(8): 3545–3553
|
15 |
Duitama J, Srivastava P K, Măndoiu I I (2012). Towards accurate detection and genotyping of expressed variants from whole transcriptome sequencing data. BMC Genomics, 13(2 Suppl 2): S6
|
16 |
Feng J, Meyer C A, Wang Q, Liu J S, Shirley Liu X, Zhang Y (2012). GFOLD: a generalized fold change for ranking differentially expressed genes from RNA-seq data. Bioinformatics, 28(21): 2782–2788
|
17 |
Foley E J (1953). Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Res, 13(12): 835–837
|
18 |
Gubin M M, Zhang X, Schuster H, Caron E, Ward J P, Noguchi T, Ivanova Y, Hundal J, Arthur C D, Krebber W J, Mulder G E, Toebes M, Vesely M D, Lam S S, Korman A J, Allison J P, Freeman G J, Sharpe A H, Pearce E L, Schumacher T N, Aebersold R, Rammensee H G, Melief C J, Mardis E R, Gillanders W E, Artyomov M N, Schreiber R D (2014). Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature, 515(7528): 577–581
|
19 |
Kim D, Langmead B, Salzberg S L (2015). HISAT: a fast spliced aligner with low memory requirements. Nat Methods, 12(4): 357–360
|
20 |
Langmead B, Trapnell C, Pop M, Salzberg S L (2009). Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol, 10(3): R25
|
21 |
Larsen M V, Lundegaard C, Lamberth K, Buus S, Lund O, Nielsen M (2007). Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinformatics, 8(1): 424
|
22 |
Li B, Dewey C N (2011). RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics, 12(1): 323
|
23 |
Liu J, Blake S J, Smyth M J, Teng M W (2014). Improved mouse models to assess tumour immunity and irAEs after combination cancer immunotherapies. Clin Transl Immunology, 3(8): e22
|
24 |
Lundegaard C, Lund O, Nielsen M (2008). Accurate approximation method for prediction of class I MHC affinities for peptides of length 8, 10 and 11 using prediction tools trained on 9mers. Bioinformatics, 24(11): 1397–1398
|
25 |
Lurquin C, Van Pel A, Mariamé B, De Plaen E, Szikora J P, Janssens C, Reddehase M J, Lejeune J, Boon T (1989). Structure of the gene of tum- transplantation antigen P91A: the mutated exon encodes a peptide recognized with Ld by cytolytic T cells. Cell, 58(2): 293–303
|
26 |
Matsushita H, Vesely M D, Koboldt D C, Rickert C G, Uppaluri R, Magrini V J, Arthur C D, White J M, Chen Y S, Shea L K, Hundal J, Wendl M C, Demeter R, Wylie T, Allison J P, Smyth M J, Old L J, Mardis E R, Schreiber R D (2012). Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature, 482(7385): 400–404
|
27 |
McGranahan N, Furness A J, Rosenthal R, Ramskov S, Lyngaa R, Saini S K, Jamal-Hanjani M, Wilson G A, Birkbak N J, Hiley C T, Watkins T B, Shafi S, Murugaesu N, Mitter R, Akarca A U, Linares J, Marafioti T, Henry J Y, Van Allen E M, Miao D, Schilling B, Schadendorf D, Garraway L A, Makarov V, Rizvi N A, Snyder A, Hellmann M D, Merghoub T, Wolchok J D, Shukla S A, Wu C J, Peggs K S, Chan T A, Hadrup S R, Quezada S A, Swanton C (2016). Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science, 351(6280): 1463–1469
|
28 |
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo M A (2010). The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res, 20(9): 1297–1303
|
29 |
Monach P A, Meredith S C, Siegel C T, Schreiber H (1995). A unique tumor antigen produced by a single amino acid substitution. Immunity, 2(1): 45–59
|
30 |
Nicolae M, Mangul S, Măndoiu I I, Zelikovsky A (2011). Estimation of alternative splicing isoform frequencies from RNA-Seq data. Algorithms Mol Biol, 6(1): 9
|
31 |
Noguchi Y, Chen Y T, Old L J (1994). A mouse mutant p53 product recognized by CD4+ and CD8+ T cells. Proc Natl Acad Sci USA, 91(8): 3171–3175
|
32 |
Nowell P C (1976). The clonal evolution of tumor cell populations. Science, 194(4260): 23–28
|
33 |
Pandey V, Nutter R C, Prediger E ( 2008).Applied Biosystems SOLiD™ System: Ligation-Based Sequencing. In: Janitz M, ed. Next Generation Genome Sequencing. Wiley-VCH Verlag GmbH & Co. KGaA. p. 29–42
|
34 |
Prehn R T, Main J M (1957). Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst, 18(6): 769–778
|
35 |
Roberts A, Trapnell C, Donaghey J, Rinn J L, Pachter L (2011). Improving RNA-Seq expression estimates by correcting for fragment bias. Genome Biol, 12(3): R22
|
36 |
Robinson M D, McCarthy D J, Smyth G K (2010). edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics, 26(1): 139–140
|
37 |
Schmieder R, Edwards R (2011). Quality control and preprocessing of metagenomic datasets. Bioinformatics, 27(6): 863–864
|
38 |
Schuler M M, Nastke M D, Stevanovikć S (2007). SYFPEITHI: database for searching and T-cell epitope prediction. Methods Mol Biol, 409: 75–93
|
39 |
Srivastava P K (2015). Neoepitopes of Cancers: Looking Back, Looking Ahead. Cancer Immunol Res, 3(9): 969–977
|
40 |
Thomas R K, Nickerson E, Simons J F, Jänne P A, Tengs T, Yuza Y, Garraway L A, LaFramboise T, Lee J C, Shah K, O’Neill K, Sasaki H, Lindeman N, Wong K K, Borras A M, Gutmann E J, Dragnev K H, DeBiasi R, Chen T H, Glatt K A, Greulich H, Desany B, Lubeski C K, Brockman W, Alvarez P, Hutchison S K, Leamon J H, Ronan M T, Turenchalk G S, Egholm M, Sellers W R, Rothberg J M, Meyerson M (2006). Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing. Nat Med, 12(7): 852–855
|
41 |
Tian S, Maile R, Collins E J, Frelinger J A (2007). CD8+ T cell activation is governed by TCR-peptide/MHC affinity, not dissociation rate. J Immunol, 179(5): 2952–2960
|
42 |
Trapnell C, Pachter L, Salzberg S L (2009). TopHat: discovering splice junctions with RNA-Seq. Bioinformatics, 25(9): 1105–1111
|
43 |
Yadav M, Jhunjhunwala S, Phung Q T, Lupardus P, Tanguay J, Bumbaca S, Franci C, Cheung T K, Fritsche J, Weinschenk T, Modrusan Z, Mellman I, Lill J R, Delamarre L (2014). Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature, 515(7528): 572–576
|
44 |
Yates L R, Campbell P J (2012). Evolution of the cancer genome. Nat Rev Genet, 13(11): 795–806
|
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