DIMEimmune: Robust estimation of infiltrating lymphocytes in CNS tumors from DNA methylation profiles

References

• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–14. doi:10.1016/j.cell.2011.02.013.
   PubMed Web of Science ®Google Scholar
• Quail DF, Joyce JA. The Microenvironmental Landscape of Brain Tumors. Cancer Cell. 2017;31:326–341. doi:10.1016/j.ccell.2017.02.009.
   PubMed Web of Science ®Google Scholar
• Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, Vijver K V D, Estrada M V, Gonzalez-Ericsson P I, et al. Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: a Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research. Adv Anat Pathol. 2017;24:235–251. doi:10.1097/PAP.0000000000000162.
   PubMed Web of Science ®Google Scholar
• Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B,  Christie M, Vijver KVD, Estrada MV, Gonzalez-Ericsson P I, et al. Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: a Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors. Adv Anat Pathol. 2017;24:311–335. doi:10.1097/PAP.0000000000000161.
   PubMed Web of Science ®Google Scholar
• Bieńkowski M, Preusser M. Prognostic role of tumour-infiltrating inflammatory cells in brain tumours: literature review. Curr Opin Neurol. 2015;28(6):647–658. doi:10.1097/WCO.0000000000000251.
   PubMed Web of Science ®Google Scholar
• Rutledge WC, Kong J, Gao J, Gutman DA, Cooper LAD, Appin C, Park Y,  Scarpace L, Mikkelsen T, Cohen M L, et al. Tumor-infiltrating lymphocytes in glioblastoma are associated with specific genomic alterations and related to transcriptional class. Clin Cancer Res. 2013;19:4951–4960. doi:10.1158/1078-0432.CCR-13-0551.
   PubMed Web of Science ®Google Scholar
• Marinari E, Allard M, Gustave R, Widmer V, Philippin G, Merkler D, Tsantoulis P, Valérie D, Dietrich, P-Y. Inflammation and lymphocyte infiltration are associated with shorter survival in patients with high-grade glioma. Oncoimmunology. 2020;9:1779990. doi:10.1080/2162402X.2020.1779990.
   PubMed Web of Science ®Google Scholar
• Bockmayr M, Klauschen F, Maire CL, Rutkowski S, Westphal M, Lamszus K, Schüller U, Mohme M. Immunologic profiling of mutational and transcriptional subgroups in pediatric and adult high-grade gliomas. Cancer Immunol Res. 2019;7:1401–1411. doi:10.1158/2326-6066.CIR-18-0939.
   PubMed Web of Science ®Google Scholar
• Bockmayr M, Mohme M, Klauschen F, Winkler B, Budczies J, Rutkowski S, Schüller U. Subgroup-specific immune and stromal microenvironment in medulloblastoma. Oncoimmunology. 2018;7:e1462430. doi:10.1080/2162402X.2018.1462430.
   PubMed Web of Science ®Google Scholar
• Leruste A, Tosello J, Ramos RN, Tauziède-Espariat A, Brohard S, Han Z-Y, Beccaria K, Andrianteranagna M, Caudana P, Nikolic J, et al. Clonally expanded T cells reveal immunogenicity of rhabdoid tumors. Cancer Cell. 2019;36:597–612.e8. doi:10.1016/j.ccell.2019.10.008.
   PubMed Web of Science ®Google Scholar
• Griesinger AM, Josephson RJ, Donson AM, Mulcahy Levy JM, Amani V, Birks DK, Hoffman LM, Furtek SF, Reigan P, Handler MH, et al. Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma. Cancer Immunol Res. 2015;3:1165–1174. doi:10.1158/2326-6066.CIR-15-0061.
   PubMed Web of Science ®Google Scholar
• Grabovska Y, Mackay A, O’Hare P, Crosier S, Finetti M, Schwalbe EC, Pickles JC, Fairchild AR, Avery A, Cockle J, et al. Pediatric pan-central nervous system tumor analysis of immune-cell infiltration identifies correlates of antitumor immunity. Nat Commun. 2020;11:4324. doi:10.1038/s41467-020-18070-y.
   PubMed Web of Science ®Google Scholar
• Chakravarthy A, Furness A, Joshi K, Ghorani E, Ford K, Ward MJ, King EM, Lechner M, Marafioti T, Quezada SA, et al. Pan-cancer deconvolution of tumour composition using DNA methylation. Nat Commun. 2018;9:3220. doi:10.1038/s41467-018-05570-1.
   PubMed Web of Science ®Google Scholar
• Klauschen F, Müller K-R, Binder A, Bockmayr M, Hägele M, Seegerer P, Wienerta S, Prunerie G, Mariaf S de, Badve S, et al. Scoring of tumor-infiltrating lymphocytes: from visual estimation to machine learning. Semin Cancer Biol. Elsevier, 2018;151–157. doi:10.1016/j.semcancer.2018.07.001.
   PubMed Web of Science ®Google Scholar
• Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453–457. doi:10.1038/nmeth.3337.
   PubMed Web of Science ®Google Scholar
• Becht E, Giraldo NA, Lacroix L, Buttard B, Elarouci N, Petitprez F, Selves J, Laurent-Puig P, Sautès-Fridman C, Fridman WH, et al. Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol. 2016;17:218. doi:10.1186/s13059-016-1070-5.
   PubMed Web of Science ®Google Scholar
• Danaher P, Warren S, Dennis L, D’Amico L, White A, Disis ML, Geller MA, Odunsi K, Beechem J, Fling SP. Gene expression markers of Tumor Infiltrating Leukocytes. J Immunother Cancer. 2017;5:18. doi:10.1186/s40425-017-0215-8.
   PubMed Web of Science ®Google Scholar
• Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, Nair VS, Xu Y, Khuong A, Hoang CD, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med. 2015;21:938–945. doi:10.1038/nm.3909.
   PubMed Web of Science ®Google Scholar
• Ali HR, Chlon L, Pharoah PDP, Markowetz F, Caldas C. Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: a Gene-Expression-Based Retrospective Study. PLoS Med. 2016;13:e1002194. doi:10.1371/journal.pmed.1002194.
   PubMed Web of Science ®Google Scholar
• Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, Gröbner S, Segura-Wang M, Zichner T, Rudneva VA, et al. Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer Cell. 2017;31(737–754.e6). doi:10.1016/j.ccell.2017.05.005.
   PubMedGoogle Scholar
• Northcott PA, Buchhalter I, Morrissy AS, Hovestadt V, Weischenfeldt J, Ehrenberger T, et al. The whole-genome landscape of medulloblastoma subtypes. Nature. 2017;547:311–317. doi:10.1038/nature22973.
   PubMed Web of Science ®Google Scholar
• Pajtler KW, Witt H, Sill M, Jones DTW, Hovestadt V, Kratochwil F, Wani K, Tatevossian R, Punchihewa C, Johann P, et al. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell. 2015;27:728–743. doi:10.1016/j.ccell.2015.04.002.
   PubMed Web of Science ®Google Scholar
• Torchia J, Golbourn B, Feng S, Ho KC, Sin-Chan P, Vasiljevic A, Norman JD, Guilhamon P, Garzia L, Agamez NR, et al. Integrated (epi)-genomic analyses identify subgroup-specific therapeutic targets in CNS Rhabdoid Tumors. Cancer Cell. 2016;30:891–908. doi:10.1016/j.ccell.2016.11.003.
   PubMed Web of Science ®Google Scholar
• Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, Capper D, Sill M, Buchhalter I, Northcott PA, Leis I, Ryzhova M, et al. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell. 2016;164:1060–1072. doi:10.1016/j.cell.2016.01.015.
   PubMed Web of Science ®Google Scholar
• Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, Koelsche C, Sahm F, Chavez L, Reuss DE, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018;555:469–474. doi:10.1038/nature26000.
   PubMed Web of Science ®Google Scholar
• Jurmeister P, Bockmayr M, Seegerer P, Bockmayr T, Treue D, Montavon G, Vollbrecht C, Arnold A, Teichmann D, Bressem K, et al. Machine learning analysis of DNA methylation profiles distinguishes primary lung squamous cell carcinomas from head and neck metastases. Sci Transl Med. 2019;11: doi:10.1126/scitranslmed.aaw8513.
   PubMed Web of Science ®Google Scholar
• Orozco JIJ, Knijnenburg TA, Manughian-Peter AO, Salomon MP, Barkhoudarian G, Jalas JR, Wilmott JS, Hothi P, Wang X, Takasumi Y, et al. Epigenetic profiling for the molecular classification of metastatic brain tumors. Nat Commun. 2018;9:4627. doi:10.1038/s41467-018-06715-y.
   PubMed Web of Science ®Google Scholar
• Moran S, Martínez-Cardús A, Sayols S, Musulén E, Balañá C, Estival-Gonzalez A, Moutinho C, Heyn H, Diaz-Lagares A, Castro de Moura M, et al. Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. Lancet Oncol. 2016;17:1386–1395. doi:10.1016/S1470-2045(16)30297-2.
   PubMed Web of Science ®Google Scholar
• Jeschke J, Bizet M, Desmedt C, Calonne E, Dedeurwaerder S, Garaud S, Koch A, Larsimont D, Salgado R, Van den Eynden G, et al. DNA methylation-based immune response signature improves patient diagnosis in multiple cancers. J Clin Invest. 2017;127:3090–3102. doi:10.1172/JCI91095.
   PubMed Web of Science ®Google Scholar
• The R Core Team. R: a language and environment for statistical computing. 2019; Available from: https://www.r-project.org/
   Google Scholar
• Aryee MJ, Jaffe AE, Corrada-Bravo H, Ladd-Acosta C, Feinberg AP, Hansen KD, Irizarry RA, Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30:1363–1369. doi:10.1093/bioinformatics/btu049.
   PubMed Web of Science ®Google Scholar
• Phipson B, Maksimovic J, Oshlack A. missMethyl: an R package for analyzing data from Illumina’s HumanMethylation450 platform. Bioinformatics. 2016;32(2):286–288. doi:10.1093/bioinformatics/btv560.
   PubMed Web of Science ®Google Scholar
• Gu Z, Eils R, Schlesner M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics. 2016;32(18):2847–2849. doi:10.1093/bioinformatics/btw313.
   PubMed Web of Science ®Google Scholar
• Colaprico A, Silva TC, Olsen C, Garofano L, Cava C, Garolini D, Sabedot TS, Malta TM, Pagnotta SM, Castiglioni I, et al. TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res. 2016;44:e71. doi:10.1093/nar/gkv1507.
   PubMed Web of Science ®Google Scholar
• Therneau TM, Grambsch PM Modeling Survival Data: extending the Cox Model [Internet]. Springer-Verlag:New York. 2000 [ cited 2020 Sep 23]. Available from: https://www.springer.com/gp/book/9780387987842
   Google Scholar
• FlowSorted.Blood.450k [Internet]. Bioconductor. [cited 2020 Sep 23]. Available from: http://bioconductor.org/packages/FlowSorted.Blood.450k/
   Google Scholar
• Eklund A. beeswarm: the Bee Swarm Plot, an Alternative to Stripchart [Internet]. 2016 [ cited 2020 Sep 23]. Available from: https://CRAN.R-project.org/package=beeswarm
   Google Scholar
• Ripley B, Venables B, Bates DM, ca 1998) KH (partial port, ca 1998) AG (partial port, Firth D. MASS: support Functions and Datasets for Venables and Ripley’s MASS [Internet]. 2020 [cited 2020 Sep 23]. Available from: https://CRAN.R-project.org/package=MASS
   Google Scholar
• Du P, Kibbe WA, Lin SM. lumi: a pipeline for processing Illumina microarray. Bioinformatics. 2008;24(13):1547–1548. doi:10.1093/bioinformatics/btn224.
   PubMed Web of Science ®Google Scholar
• Tserel L, Kolde R, Limbach M, Tretyakov K, Kasela S, Kisand K, Saare M, Vilo J, Metspalu A, Milani L, et al. Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes. Sci Rep. 2015;5:13107. doi:10.1038/srep13107.
   PubMed Web of Science ®Google Scholar
• Edgar R, Domrachev M, Lash AE. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002;30:207–210. doi:10.1093/nar/30.1.207.
   PubMed Web of Science ®Google Scholar
• Torchia J, Picard D, Lafay-Cousin L, Hawkins CE, Kim S-K, Letourneau L, Ra Y-S, Ching Ho K, Yu Chan TS, Sin-Chan P, et al. Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis. Lancet Oncol. 2015;16:569–582. doi:10.1016/S1470-2045(15)70114-2.
   PubMed Web of Science ®Google Scholar
• Ceccarelli M, Barthel FP, Malta TM, Sabedot TS, Salama SR, Murray BA, Morozova O, Yulia Newton Y, Radenbaugh A, Pagnotta SM, et al. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. Cell. 2016;164:550–563. doi:10.1016/j.cell.2015.12.028.
   PubMed Web of Science ®Google Scholar
• Rahman M, Jackson LK, Johnson WE, Li DY, Bild AH, Piccolo SR. Alternative preprocessing of RNA-Sequencing data in The Cancer Genome Atlas leads to improved analysis results. Bioinformatics. 2015;31:3666–3672. doi:10.1093/bioinformatics/btv377.
   PubMed Web of Science ®Google Scholar
• Gautier L, Cope L, Bolstad BM, Irizarry RA. affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004;20:307–315. doi:10.1093/bioinformatics/btg405.
   PubMed Web of Science ®Google Scholar
• Dai M, Wang P, Boyd AD, Kostov G, Athey B, Jones EG, Bunney WE, Myers RM, Speed TP, Akil H, et al. Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res. 2005;33:e175. doi:10.1093/nar/gni179.
   PubMed Web of Science ®Google Scholar
• Reinius LE, Acevedo N, Joerink M, Pershagen G, S-e D, Greco D, Söderhäll C, Scheynius A, Kere J. Differential DNA Methylation in Purified Human Blood Cells: implications for Cell Lineage and Studies on Disease Susceptibility. PLOS ONE. 2012;7:e41361. doi:10.1371/journal.pone.0041361.
   PubMed Web of Science ®Google Scholar
• Wang Q, Hu B, Hu X, Kim H, Squatrito M, Scarpace L, deCarvalho AC, Lyu S, Li P, Li Y, et al. Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. Cancer Cell. 2017;32(42–56.e6). doi:10.1016/j.ccell.2017.06.003.
   Google Scholar
• Capper D, Stichel D, Sahm F, Jones DTW, Schrimpf D, Sill M, Schmid S, Hovestadt V, Reuss DE, Koelsche C, et al. Practical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experience. Acta Neuropathol. 2018;136:181–210. doi:10.1007/s00401-018-1879-y.
   PubMed Web of Science ®Google Scholar
• Pickles JC, Stone TJ, Jacques TS. Methylation-based algorithms for diagnosis: experience from neuro-oncology. J Pathol. 2020;250(5):510–517. doi:10.1002/path.5397.
   PubMed Web of Science ®Google Scholar
• Vermeulen JF, Van Hecke W, Adriaansen EJM, Jansen MK, Bouma RG, Villacorta Hidalgo J, Fisch P, Broekhuizen R, Spliet WGM, Kool M, et al. Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma. Oncoimmunology. 2017;7. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790383/.
   PubMed Web of Science ®Google Scholar
• Margol AS, Robison NJ, Gnanachandran J, Hung LT, Kennedy RJ, Vali M, Dhall G,  Finlay JL, Erdreich-Epstein A, Krieger MD, et al. Tumor-associated macrophages in SHH subgroup of medulloblastomas. Clin Cancer Res. 2015;21:1457–1465. doi:10.1158/1078-0432.CCR-14-1144.
   PubMed Web of Science ®Google Scholar
• Berghoff AS, Kiesel B, Widhalm G, Wilhelm D, Rajky O, Kurscheid S, French PJ. Correlation of immune phenotype with IDH mutation in diffuse glioma. Neuro-oncology. 2017;19:1460–1468. doi:10.1093/neuonc/nox054.
   PubMed Web of Science ®Google Scholar
• Weenink B, Draaisma K, Ooi HZ, Kros JM, Pae SS, Debets R, et al. Low-grade glioma harbors few CD8 T cells, which is accompanied by decreased expression of chemo-attractants, not immunogenic antigens. Sci Rep. 2019;9:14643. doi:10.1038/s41598-019-51063-6.
   PubMed Web of Science ®Google Scholar
• Lohr J, Ratliff T, Huppertz A, Ge Y, Dictus C, Ahmadi R, Grau S, Hiraoka N, Eckstein V, Ecker RC, et al. Effector T-Cell Infiltration Positively Impacts Survival of Glioblastoma Patients and Is Impaired by Tumor-Derived TGF-β. Clin Cancer Res. 2011;17:4296–4308. doi:10.1158/1078-0432.CCR-10-2557.
   PubMed Web of Science ®Google Scholar
• Chun H-JE, Johann PD, Milne K, Zapatka M, Buellesbach A, Ishaque N, Iskar M, Erkek S, Wei L, Tessier-Cloutier B, et al. Identification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltration. Cell Rep. 2019;29(2338–2354.e7). doi:10.1016/j.celrep.2019.10.013.
   PubMedGoogle Scholar
• Hoffman LM, Donson AM, Nakachi I, Griesinger AM, Birks DK, Amani V, Hemenway MS, Liu AK, Wang M, Hankinson TC, et al. Molecular sub-group-specific immunophenotypic changes are associated with outcome in recurrent posterior fossa ependymoma. Acta Neuropathol. 2014;127:731–745. doi:10.1007/s00401-013-1212-8.
   PubMed Web of Science ®Google Scholar
• Han S, Zhang C, Li Q, Dong J, Liu Y, Huang Y, Jiang T, Wu A. Tumour-infiltrating CD4+ and CD8+ lymphocytes as predictors of clinical outcome in glioma. Br J Cancer. 2014;110:2560–2568. doi:10.1038/bjc.2014.162.
   PubMed Web of Science ®Google Scholar