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SOX2 immunity and tissue resident memory in children and young adults with glioma

  • Laboratory Investigation
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Abstract

Therapies targeting immune checkpoints are effective in tumors with a high mutation burden that express multiple neo-antigens. However, glial tumors including those seen in children carry fewer mutations and there is an unmet need to identify new antigenic targets of anti-tumor immunity. SOX2 is an embryonal stem cell antigen implicated in the biology of glioma initiating cells. Expression of SOX2 by pediatric glial tumors and the capacity of the immune system in these patients to recognize SOX2 has not been previously studied. We examined the expression of SOX2 on archived paraffin-embedded tissue from pediatric glial tumors. The presence of T-cell immunity to SOX2 was examined in both blood and tumor-infiltrating T-cells in children and young adults with glioma. The nature of tumor-infiltrating immune cells was analyzed with a 37-marker panel using single-cell mass cytometry. SOX2 is expressed by tumor cells but not surrounding normal tissue in pediatric gliomas of all grades. T-cells against this antigen can be detected in blood and tumor tissue in glioma patients. Glial tumors are enriched for CD8/CD4 T-cells with tissue resident memory (TRM; CD45RO+, CD69+, CCR7−) phenotype, which co-express multiple inhibitory checkpoints including PD-1, PD-L1 and TIGIT. Tumors also contain natural killer cells with reduced expression of lytic granzyme. Our data demonstrate immunogenicity of SOX2, which is specifically overexpressed on pediatric glial tumor cells. Harnessing tumor immunity in glioma will likely require the combined targeting of multiple inhibitory checkpoints.

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References

  1. Curtin SC, Minino AM, Anderson RN (2016) Declines in cancer death rates among children and adolescents in the United States, 1999–2014. NCHS Data Brief 257:1

    Google Scholar 

  2. Gurney JG, Kadan-Lottick NS, Packer RJ, Neglia JP, Sklar CA, Punyko JA, Stovall M, Yasui Y, Nicholson HS, Wolden S, McNeil DE, Mertens AC, Robison LL, Childhood Cancer Survivor Study (2003) Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study. Cancer 97(3):663–673. doi:10.1002/cncr.11095

    Article  PubMed  Google Scholar 

  3. Jones C, Karajannis MA, Jones DT, Kieran MW, Monje M, Baker SJ, Becher OJ, Cho YJ, Gupta N, Hawkins C, Hargrave D, Haas-Kogan DA, Jabado N, Li XN, Mueller S, Nicolaides T, Packer RJ, Persson AI, Phillips JJ, Simonds EF, Stafford JM, Tang Y, Pfister SM, Weiss WA (2016) Pediatric high-grade glioma: biologically and clinically in need of new thinking. Neuro-oncology. doi:10.1093/neuonc/now101

    Google Scholar 

  4. Pollack IF, Jakacki RI (2011) Childhood brain tumors: epidemiology, current management and future directions. Nat Rev Neurol 7(9):495–506. doi:10.1038/nrneurol.2011.110

    Article  PubMed  Google Scholar 

  5. Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, Hu-Lieskovan S, Berent-Maoz B, Pang J, Chmielowski B, Cherry G, Seja E, Lomeli S, Kong X, Kelley MC, Sosman JA, Johnson DB, Ribas A, Lo RS (2016) Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell 165(1):35–44. doi:10.1016/j.cell.2016.02.065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372(26):2509–2520. doi:10.1056/NEJMoa1500596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O’Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. doi:10.1056/NEJMoa1606774

    PubMed  Google Scholar 

  8. Johanns TM, Miller CA, Dorward IG, Tsien C, Chang E, Perry A, Uppaluri R, Ferguson C, Schmidt RE, Dahiya S, Ansstas G, Mardis ER, Dunn GP (2016) Immunogenomics of hypermutated glioblastoma: a patient with germline POLE deficiency treated with checkpoint blockade immunotherapy. Cancer Discov 6(11):1230–1236. doi:10.1158/2159-8290.cd-16-0575

    Article  PubMed  Google Scholar 

  9. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjord JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jager N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, Lopez-Otin C, Martin S, Munshi NC, Nakamura H, Northcott PA, Pajic M, Papaemmanuil E, Paradiso A, Pearson JV, Puente XS, Raine K, Ramakrishna M, Richardson AL, Richter J, Rosenstiel P, Schlesner M, Schumacher TN, Span PN, Teague JW, Totoki Y, Tutt AN, Valdes-Mas R, van Buuren MM, van‘t Veer L, Vincent-Salomon A, Waddell N, Yates LR, Zucman-Rossi J, Futreal PA, McDermott U, Lichter P, Meyerson M, Grimmond SM, Siebert R, Campo E, Shibata T, Pfister SM, Campbell PJ, Stratton MR (2013) Signatures of mutational processes in human cancer. Nature 500(7463):415–421. doi:10.1038/nature12477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bouffet E, Larouche V, Campbell BB, Merico D, de Borja R, Aronson M, Durno C, Krueger J, Cabric V, Ramaswamy V, Zhukova N, Mason G, Farah R, Afzal S, Yalon M, Rechavi G, Magimairajan V, Walsh MF, Constantini S, Dvir R, Elhasid R, Reddy A, Osborn M, Sullivan M, Hansford J, Dodgshun A, Klauber-Demore N, Peterson L, Patel S, Lindhorst S, Atkinson J, Cohen Z, Laframboise R, Dirks P, Taylor M, Malkin D, Albrecht S, Dudley RW, Jabado N, Hawkins CE, Shlien A, Tabori U (2016) Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol 34(19):2206–2211. doi:10.1200/jco.2016.66.6552

    Article  PubMed  Google Scholar 

  11. Pollack IF, Jakacki RI, Butterfield LH, Hamilton RL, Panigrahy A, Normolle DP, Connelly AK, Dibridge S, Mason G, Whiteside TL, Okada H (2016) Immune responses and outcome after vaccination with glioma-associated antigen peptides and poly-ICLC in a pilot study for pediatric recurrent low-grade gliomas. Neuro-oncology 18(8):1157–1168. doi:10.1093/neuonc/now026

    Article  PubMed  PubMed Central  Google Scholar 

  12. Platten M, Bunse L, Wick W, Bunse T (2016) Concepts in glioma immunotherapy. Cancer Immunol Immunother 65 (10):1269–1275. doi:10.1007/s00262-016-1874-x

    Article  CAS  PubMed  Google Scholar 

  13. Kahlon KS, Brown C, Cooper LJ, Raubitschek A, Forman SJ, Jensen MC (2004) Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells. Cancer Res 64(24):9160–9166. doi:10.1158/0008-5472.can-04-0454

    Article  CAS  PubMed  Google Scholar 

  14. Sarkar A, Hochedlinger K (2013) The sox family of transcription factors: versatile regulators of stem and progenitor cell fate. Cell Stem Cell 12(1):15–30. doi:10.1016/j.stem.2012.12.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Graham V, Khudyakov J, Ellis P, Pevny L (2003) SOX2 functions to maintain neural progenitor identity. Neuron 39(5):749–765

    Article  CAS  PubMed  Google Scholar 

  16. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401. doi:10.1038/nature03128

    Article  CAS  PubMed  Google Scholar 

  17. Tam WL, Ng HH (2014) Sox2: masterminding the root of cancer. Cancer cell 26(1):3–5. doi:10.1016/j.ccr.2014.06.024

    Article  CAS  PubMed  Google Scholar 

  18. Gangemi RM, Griffero F, Marubbi D, Perera M, Capra MC, Malatesta P, Ravetti GL, Zona GL, Daga A, Corte G (2009) SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity. Stem Cells 27(1):40–48. doi:10.1634/stemcells.2008-0493

    Article  CAS  PubMed  Google Scholar 

  19. Berezovsky AD, Poisson LM, Cherba D, Webb CP, Transou AD, Lemke NW, Hong X, Hasselbach LA, Irtenkauf SM, Mikkelsen T, deCarvalho AC (2014) Sox2 promotes malignancy in glioblastoma by regulating plasticity and astrocytic differentiation. Neoplasia 16(3):193–206, 206 e119–206 e125. doi:10.1016/j.neo.2014.03.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444(7120):756–760. doi:10.1038/nature05236

    Article  CAS  PubMed  Google Scholar 

  21. Auffinger B, Tobias AL, Han Y, Lee G, Guo D, Dey M, Lesniak MS, Ahmed AU (2014) Conversion of differentiated cancer cells into cancer stem-like cells in a glioblastoma model after primary chemotherapy. Cell Death Differ 21(7):1119–1131. doi:10.1038/cdd.2014.31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Auffinger B, Spencer D, Pytel P, Ahmed AU, Lesniak MS (2015) The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence. Expert Rev Neurother 15(7):741–752. doi:10.1586/14737175.2015.1051968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schmitz M, Temme A, Senner V, Ebner R, Schwind S, Stevanovic S, Wehner R, Schackert G, Schackert HK, Fussel M, Bachmann M, Rieber EP, Weigle B (2007) Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy. Br J Cancer 96(8):1293–1301. doi:10.1038/sj.bjc.6603696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Polakova I, Duskova M, Smahel M (2014) Antitumor DNA vaccination against the Sox2 transcription factor. Int J Oncol 45(1):139–146. doi:10.3892/ijo.2014.2402

    CAS  PubMed  Google Scholar 

  25. Boddupalli CS, Bar N, Kadaveru K, Krauthammer M, Pornputtapong N, Mai Z, Ariyan S, Narayan D, Kluger H, Deng Y, Verma R, Das R, Bacchiocchi A, Halaban R, Sznol M, Dhodapkar MV, Dhodapkar KM (2016) Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells. JCI Insight 1(21):e88955. doi:10.1172/jci.insight.88955

    Article  PubMed  PubMed Central  Google Scholar 

  26. Amir ED, Davis KL, Tadmor MD, Simonds EF, Levine JH, Bendall SC, Shenfeld DK, Krishnaswamy S, Nolan GP, Pe’er D (2013) viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat Biotechnol 31(6):545–552. doi:10.1038/nbt.2594

    Article  CAS  PubMed Central  Google Scholar 

  27. Spisek R, Kukreja A, Chen LC, Matthews P, Mazumder A, Vesole D, Jagannath S, Zebroski HA, Simpson AJ, Ritter G, Durie B, Crowley J, Shaughnessy JD Jr, Scanlan MJ, Gure AO, Barlogie B, Dhodapkar MV (2007) Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy. J Exp Med 204(4):831–840. doi:10.1084/jem.20062387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dhodapkar KM, Feldman D, Matthews P, Radfar S, Pickering R, Turkula S, Zebroski H, Dhodapkar MV (2010) Natural immunity to pluripotency antigen OCT4 in humans. Proc Natl Acad Sci USA 107(19):8718–8723. doi:10.1073/pnas.0915086107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Annovazzi L, Mellai M, Caldera V, Valente G, Schiffer D (2011) SOX2 expression and amplification in gliomas and glioma cell lines. Cancer Genomics Proteomics 8(3):139–147

    CAS  PubMed  Google Scholar 

  30. Phi JH, Park SH, Kim SK, Paek SH, Kim JH, Lee YJ, Cho BK, Park CK, Lee DH, Wang KC (2008) Sox2 expression in brain tumors: a reflection of the neuroglial differentiation pathway. Am J Surg Pathol 32(1):103–112. doi:10.1097/PAS.0b013e31812f6ba6

    Article  PubMed  Google Scholar 

  31. Lee C, Fotovati A, Triscott J, Chen J, Venugopal C, Singhal A, Dunham C, Kerr JM, Verreault M, Yip S, Wakimoto H, Jones C, Jayanthan A, Narendran A, Singh SK, Dunn SE (2012) Polo-like kinase 1 inhibition kills glioblastoma multiforme brain tumor cells in part through loss of SOX2 and delays tumor progression in mice. Stem Cells 30(6):1064–1075. doi:10.1002/stem.1081

    Article  CAS  PubMed  Google Scholar 

  32. Dhodapkar KM, Gettinger SN, Das R, Zebroski H, Dhodapkar MV (2013) SOX2-specific adaptive immunity and response to immunotherapy in non-small cell lung cancer. Oncoimmunology 2(7):e25205. doi:10.4161/onci.25205

    Article  PubMed  PubMed Central  Google Scholar 

  33. Dhodapkar MV, Sexton R, Das R, Dhodapkar KM, Zhang L, Sundaram R, Soni S, Crowley JJ, Orlowski RZ, Barlogie B (2015) Prospective analysis of antigen-specific immunity, stem-cell antigens, and immune checkpoints in monoclonal gammopathy. Blood 126(22):2475–2478. doi:10.1182/blood-2015-03-632919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Parney IF, Waldron JS, Parsa AT (2009) Flow cytometry and in vitro analysis of human glioma-associated macrophages. Laboratory investigation. J Neurosurg 110(3):572–582. doi:10.3171/2008.7.JNS08475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Reni M, Mazza E, Zanon S, Gatta G, Vecht CJ (2017) Central nervous system gliomas. Crit Rev Oncol Hematol 113:213–234. doi:10.1016/j.critrevonc.2017.03.021

    Article  PubMed  Google Scholar 

  36. Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DA, Tonjes M, Hovestadt V, Albrecht S, Kool M, Nantel A, Konermann C, Lindroth A, Jager N, Rausch T, Ryzhova M, Korbel JO, Hielscher T, Hauser P, Garami M, Klekner A, Bognar L, Ebinger M, Schuhmann MU, Scheurlen W, Pekrun A, Fruhwald MC, Roggendorf W, Kramm C, Durken M, Atkinson J, Lepage P, Montpetit A, Zakrzewska M, Zakrzewski K, Liberski PP, Dong Z, Siegel P, Kulozik AE, Zapatka M, Guha A, Malkin D, Felsberg J, Reifenberger G, von Deimling A, Ichimura K, Collins VP, Witt H, Milde T, Witt O, Zhang C, Castelo-Branco P, Lichter P, Faury D, Tabori U, Plass C, Majewski J, Pfister SM, Jabado N (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482(7384):226–231. doi:10.1038/nature10833

    Article  CAS  PubMed  Google Scholar 

  37. Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R, Parker M, Zhang J, Gajjar A, Dyer MA, Mullighan CG, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW, Zhang J, Baker SJ (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44(3):251–253. doi:10.1038/ng.1102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH, Beroukhim R, Bernard B, Wu CJ, Genovese G, Shmulevich I, Barnholtz-Sloan J, Zou L, Vegesna R, Shukla SA, Ciriello G, Yung WK, Zhang W, Sougnez C, Mikkelsen T, Aldape K, Bigner DD, Van Meir EG, Prados M, Sloan A, Black KL, Eschbacher J, Finocchiaro G, Friedman W, Andrews DW, Guha A, Iacocca M, O’Neill BP, Foltz G, Myers J, Weisenberger DJ, Penny R, Kucherlapati R, Perou CM, Hayes DN, Gibbs R, Marra M, Mills GB, Lander E, Spellman P, Wilson R, Sander C, Weinstein J, Meyerson M, Gabriel S, Laird PW, Haussler D, Getz G, Chin L, Network TR (2013) The somatic genomic landscape of glioblastoma. Cell 155(2):462–477. doi:10.1016/j.cell.2013.09.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT, Watkins TB, Shafi S, Murugaesu N, Mitter R, Akarca AU, Linares J, Marafioti T, Henry JY, Van Allen EM, Miao D, Schilling B, Schadendorf D, Garraway LA, Makarov V, Rizvi NA, Snyder A, Hellmann MD, Merghoub T, Wolchok JD, Shukla SA, Wu CJ, Peggs KS, Chan TA, Hadrup SR, Quezada SA, Swanton C (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351(6280):1463–1469. doi:10.1126/science.aaf1490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Alonso MM, Diez-Valle R, Manterola L, Rubio A, Liu D, Cortes-Santiago N, Urquiza L, Jauregi P, Lopez de Munain A, Sampron N, Aramburu A, Tejada-Solis S, Vicente C, Odero MD, Bandres E, Garcia-Foncillas J, Idoate MA, Lang FF, Fueyo J, Gomez-Manzano C (2011) Genetic and epigenetic modifications of Sox2 contribute to the invasive phenotype of malignant gliomas. PLoS ONE 6(11):e26740. doi:10.1371/journal.pone.0026740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676. doi:10.1016/j.cell.2006.07.024

    Article  CAS  PubMed  Google Scholar 

  42. Galon J, Fox BA, Bifulco CB, Masucci G, Rau T, Botti G, Marincola FM, Ciliberto G, Pages F, Ascierto PA, Capone M (2016) Immunoscore and Immunoprofiling in cancer: an update from the melanoma and immunotherapy bridge 2015. J Transl Med 14:273. doi:10.1186/s12967-016-1029-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Griesinger AM, Birks DK, Donson AM, Amani V, Hoffman LM, Waziri A, Wang M, Handler MH, Foreman NK (2013) Characterization of distinct immunophenotypes across pediatric brain tumor types. J Immunol 191(9):4880–4888. doi:10.4049/jimmunol.1301966

    Article  CAS  PubMed  Google Scholar 

  44. Schenkel JM, Masopust D (2014) Tissue-resident memory T cells. Immunity 41(6):886–897. doi:10.1016/j.immuni.2014.12.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Park CO, Kupper TS (2015) The emerging role of resident memory T cells in protective immunity and inflammatory disease. Nat Med 21(7):688–697. doi:10.1038/nm.3883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sathaliyawala T, Kubota M, Yudanin N, Turner D, Camp P, Thome JJ, Bickham KL, Lerner H, Goldstein M, Sykes M, Kato T, Farber DL (2013) Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. Immunity 38(1):187–197. doi:10.1016/j.immuni.2012.09.020

    Article  CAS  PubMed  Google Scholar 

  47. Wakim LM, Woodward-Davis A, Bevan MJ (2010) Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence. Proc Natl Acad Sci USA 107(42):17872–17879. doi:10.1073/pnas.1010201107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kmiecik J, Poli A, Brons NH, Waha A, Eide GE, Enger PO, Zimmer J, Chekenya M (2013) Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level. J Neuroimmunol 264(1–2):71–83. doi:10.1016/j.jneuroim.2013.08.013

    Article  CAS  PubMed  Google Scholar 

  49. Crane CA, Han SJ, Barry JJ, Ahn BJ, Lanier LL, Parsa AT (2010) TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8(+) T cells glioma patients. Neuro-oncology 12(1):7–13. doi:10.1093/neuonc/nop009

    Article  CAS  PubMed  Google Scholar 

  50. Navarro AG, Kmiecik J, Leiss L, Zelkowski M, Engelsen A, Bruserud O, Zimmer J, Enger PO, Chekenya M (2014) NK cells with KIR2DS2 immunogenotype have a functional activation advantage to efficiently kill glioblastoma and prolong animal survival. J Immunol 193(12):6192–6206. doi:10.4049/jimmunol.1400859

    Article  Google Scholar 

  51. Sehgal K, Ragheb R, Fahmy TM, Dhodapkar MV, Dhodapkar KM (2014) Nanoparticle-mediated combinatorial targeting of multiple human dendritic cell (DC) subsets leads to enhanced T cell activation via IL-15-dependent DC crosstalk. J Immunol 193(5):2297–2305. doi:10.4049/jimmunol.1400489

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Peptide synthesis was performed by Henry Zebroski at the Proteomics Resource Center of The Rockefeller University.

Funding

This study was supported in part by the Tap Cancer Out St. Baldrick’s Fellow Research Grant and National Institutes of Health training Grant T32HD068201 (J.C.V), and National Institutes of Health Grant RO1-AI0792222 and Hyundai Hope on Wheels award (K.M.D).

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Authors and Affiliations

  1. Department of Pediatrics, Yale School of Medicine, 333 Cedar Street, LMP 2073, New Haven, CT, 06510, USA

    Juan C. Vasquez, Asher Marks & Kavita M. Dhodapkar

  2. Department of Pathology, Yale School of Medicine, New Haven, CT, USA

    Anita Huttner

  3. Department of Medicine, Yale School of Medicine, New Haven, CT, USA

    Lin Zhang, Amy Chan & Joachim M. Baehring

  4. Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA

    Kristopher T. Kahle

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  1. Juan C. Vasquez
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Vasquez, J.C., Huttner, A., Zhang, L. et al. SOX2 immunity and tissue resident memory in children and young adults with glioma. J Neurooncol 134, 41–53 (2017). https://doi.org/10.1007/s11060-017-2515-8

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