Cancer Immunology, Immunotherapy

, Volume 58, Issue 10, pp 1609–1626 | Cite as

Unconventional cytokine profiles and development of T cell memory in long-term survivors after cancer vaccination

  • Jon Amund KyteEmail author
  • Sissel Trachsel
  • Bente Risberg
  • Per thor Straten
  • Kari Lislerud
  • Gustav Gaudernack
Original Article


Cancer vaccine trials frequently report on immunological responses, without any clinical benefit. This paradox may reflect the challenge of discriminating between effective and pointless immune responses and sparse knowledge on their long-term development. Here, we have analyzed T cell responses in long-term survivors after peptide vaccination. There were three main study aims: (1) to characterize the immune response in patients with a possible clinical benefit. (2) To analyze the long-term development of responses and effects of booster vaccination. (3) To investigate whether the Th1/Th2-delineation applies to cancer vaccine responses. T cell clones were generated from all nine patients studied. We find that surviving patients harbor durable tumor-specific responses against vaccine antigens from telomerase, RAS or TGFβ receptor II. Analyses of consecutive samples suggest that booster vaccination is required to induce robust T cell memory. The responses exhibit several features of possible clinical advantage, including combined T-helper and cytotoxic functionality, recognition of naturally processed antigens and diverse HLA-restriction and fine-specificity. CD4CD8 T cell clones display unconventional cytotoxicity and specifically kill tumor cells expressing mutated TGFβ receptor II. Cytokine profiling on the long-term survivors demonstrates high IFNγ/IL10-ratios, favoring immunity over tolerance, and secretion of multiple chemokines likely to mobilize the innate and adaptive immune system. Interestingly, these pro-inflammatory cytokine profiles do not follow a Th1/Th2-delineation. Most IFNγhigh/IL4low/IL10low cultures include high concentrations of hallmark Th2-cytokines IL-5 and IL-13. This does not reflect a mixture of Th1- and Th2-clones, but applies to 19/20 T cell clones confirmed to be monoclonal through TCR clonotype mapping. The present study identifies several factors that may promote clinical efficacy and suggests that cytokine profiling should not rely on the Th1/Th2-paradigm, but assess the overall inflammatory milieu and the balance between key cytokines.


Cancer vaccination Human Th1/Th2 Cytokines Clinical efficacy T cell memory 



Transforming growth factor β receptor II


Human telomerase reverse transcriptase


Denaturating gradient gel electrophoresis


Interleukin 1 receptor antagonist


Platelet derived growth factor


Fibroblast growth factor basic


Vascular endothelial growth factor


Tumor antigen


Interferon-inducible protein-10



This work was supported by the Norwegian Cancer Society and ENACT. The authors thank doctors and nurses at the study hospitals for excellent clinical follow-up and patient care. Special thanks to S. Aamdal, P. Brunsvig, T. Buanes, B. Solheim, I.K. Bukholm, L.R. Braathen, M. Gjertsen and A. Bakka. We also thank H.G. Russnes, H. Vaalerhaugen and T. Seremet for valuable help on TCR clonotype mapping.

Supplementary material

262_2009_670_MOESM1_ESM.pdf (1.9 mb)
Supplementary Figures (PDF 1957 kb)


  1. 1.
    Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M (1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549–554PubMedCrossRefGoogle Scholar
  2. 2.
    Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Fili L, Ferri S, Frosali F, Giudici F, Romagnani P, Parronchi P, Tonelli F, Maggi E, Romagnani S (2007) Phenotypic and functional features of human Th17 cells. J Exp Med 204:1849–1861PubMedCrossRefGoogle Scholar
  3. 3.
    Balkwill F (2004) Cancer and the chemokine network. Nat Rev Cancer 4:540–550PubMedCrossRefGoogle Scholar
  4. 4.
    Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, Pineiro L, Steinman R, Fay J (2001) Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res 61:6451–6458PubMedGoogle Scholar
  5. 5.
    Banchereau J, Palucka AK (2005) Dendritic cells as therapeutic vaccines against cancer. Nat Rev Cancer 5:296–306Google Scholar
  6. 6.
    Bernhardt SL, Gjertsen MK, Trachsel S, Moller M, Eriksen JA, Meo M, Buanes T, Gaudernack G (2006) Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose escalating phase I/II study. Br J Cancer 95:1474–1482PubMedCrossRefGoogle Scholar
  7. 7.
    Betts MR, Nason MC, West SM, De Rosa SC, Migueles SA, Abraham J, Lederman MM, Benito JM, Goepfert PA, Connors M, Roederer M, Koup RA (2006) HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107:4781–4789PubMedCrossRefGoogle Scholar
  8. 8.
    Bijker MS, Melief CJ, Offringa R, van der Burg SH (2007) Design and development of synthetic peptide vaccines: past, present and future. Expert Rev Vaccines 6:591–603PubMedCrossRefGoogle Scholar
  9. 9.
    Brunsvig P, Aamdal S, Gjertsen MK, Kvalheim G, Markowski-Grimsrud CJ, Sve I, Dyrhaug M, Trachsel S, Moeller M, Eriksen JA, Gaudernack G (2006) Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer. Cancer Immunol Immunother 55:1553–1564PubMedCrossRefGoogle Scholar
  10. 10.
    Butturini G, Stocken DD, Wente MN, Jeekel H, Klinkenbijl JH, Bakkevold KE, Takada T, Amano H, Dervenis C, Bassi C, Buchler MW, Neoptolemos JP (2008) Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials. Arch Surg 143:75–83PubMedCrossRefGoogle Scholar
  11. 11.
    Chaouat G, Ledée-Bataille N, Dubanchet S, Zourbas S, Sandra O, Martal J (2004) TH1/TH2 paradigm in pregnancy: paradigm lost? Int Arch Allergy Immunol 134:93–119PubMedCrossRefGoogle Scholar
  12. 12.
    Chen YX, Man K, Ling GS, Chen Y, Sun BS, Cheng Q, Wong OH, Lo CK, Ng IO, Chan LC, Lau GK, Lin CL, Huang F, Huang FP (2007) A crucial role for dendritic cell (DC) IL-10 in inhibiting successful DC-based immunotherapy: superior antitumor immunity against hepatocellular carcinoma evoked by DC devoid of IL-10. J Immunol 179:6009–6015PubMedGoogle Scholar
  13. 13.
    Darrah PA, Patel DT, De Luca PM, Lindsay RW, Davey DF, Flynn BJ, Hoff ST, Andersen P, Reed SG, Morris SL, Roederer M, Seder RA (2007) Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med 13:843–850PubMedCrossRefGoogle Scholar
  14. 14.
    De Vleeschouwer S, Spencer Lopes I, Ceuppens JL, Van Gool SW (2007) Persistent IL-10 production is required for glioma growth suppressive activity by Th1-directed effector cells after stimulation with tumor lysate-loaded dendritic cells. J Neuro-oncol 84:131–140CrossRefGoogle Scholar
  15. 15.
    Di Nicola M, Carlo-Stella C, Mortarini R, Baldassari P, Guidetti A, Gallino GF, Del Vecchio M, Ravagnani F, Magni M, Chaplin P, Cascinelli N, Parmiani G, Gianni AM, Anichini A (2004) Boosting T cell-mediated immunity to tyrosinase by vaccinia virus-transduced, CD34(+)-derived dendritic cell vaccination: a phase I trial in metastatic melanoma. Clin Cancer Res 10:5381–5390PubMedCrossRefGoogle Scholar
  16. 16.
    Domchek SM, Recio A, Mick R, Clark CE, Carpenter EL, Fox KR, DeMichele A, Schuchter LM, Leibowitz MS, Wexler MH, Vance BA, Beatty GL, Veloso E, Feldman MD, Vonderheide RH (2007) Telomerase-specific T-cell immunity in breast cancer: effect of vaccination on tumor immunosurveillance. Cancer Res 67:10546–10555PubMedCrossRefGoogle Scholar
  17. 17.
    Dong C, Flavell RA (2001) Th1 and Th2 cells. Curr Opin Hematol 8:47–51PubMedCrossRefGoogle Scholar
  18. 18.
    Dong C (2006) Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells. Nat Rev Immunol 6:329–333PubMedCrossRefGoogle Scholar
  19. 19.
    Duvall MG, Precopio ML, Ambrozak DA, Jaye A, McMichael AJ, Whittle HC, Roederer M, Rowland-Jones SL, Koup RA (2008) Polyfunctional T cell responses are a hallmark of HIV-2 infection. Eur J Immunol 38:350–363PubMedCrossRefGoogle Scholar
  20. 20.
    Fossum B, Gedde-Dahl TIII, Hansen T, Eriksen JA, Thorsby E, Gaudernack G (1993) Overlapping epitopes encompassing a point mutation (12 Gly>Arg) in p21 ras can be recognized by HLA-DR, -DP and -DQ restricted T cells. Eur J Immunol 23:2687–2691PubMedCrossRefGoogle Scholar
  21. 21.
    Fossum B, Gedde-Dahl TIII, Breivik J, Eriksen JA, Spurkland A, Thorsby E, Gaudernack G (1994) p21-ras-peptide-specific T-cell responses in a patient with colorectal cancer. CD4+ and CD8+ T cells recognize a peptide corresponding to a common mutation (13Gly>Asp). Int J Cancer 56:40–45PubMedCrossRefGoogle Scholar
  22. 22.
    Fujii S, Shimizu K, Hemmi H, Steinman RM (2007) Innate Valpha14(+) natural killer T cells mature dendritic cells, leading to strong adaptive immunity. Immunol Rev 220:183–198PubMedCrossRefGoogle Scholar
  23. 23.
    Gjertsen MK, Bjorheim J, Saeterdal I, Myklebust J, Gaudernack G (1997) Cytotoxic CD4+ and CD8+ T lymphocytes, generated by mutant p21-ras (12Val) peptide vaccination of a patient, recognize 12Val-dependent nested epitopes present within the vaccine peptide and kill autologous tumour cells carrying this mutation. Int J Cancer 72:784–790PubMedCrossRefGoogle Scholar
  24. 24.
    Gjertsen MK, Buanes T, Rosseland AR, Bakka A, Gladhaug I, Soreide O, Eriksen JA, Moller M, Baksaas I, Lothe RA, Saeterdal I, Gaudernack G (2001) Intradermal ras peptide vaccination with granulocyte–macrophage colony-stimulating factor as adjuvant: clinical and immunological responses in patients with pancreatic adenocarcinoma. Int J Cancer 92:441–450PubMedCrossRefGoogle Scholar
  25. 25.
    Gjertsen MK, Saeterdal I, Saeboe-Larssen S, Gaudernack G (2003) HLA-A3 restricted mutant ras specific cytotoxic T-lymphocytes induced by vaccination with T-helper epitopes. J Mol Med 81:43–50PubMedGoogle Scholar
  26. 26.
    Gor DO, Rose NR, Greenspan NS (2003) TH1-TH2: a procrustean paradigm. Nat Immunol 4:503–505PubMedCrossRefGoogle Scholar
  27. 27.
    Greiner TC, Raffeld M, Lutz C, Dick F, Jaffe ES (1995) Analysis of T cell receptor-gamma gene rearrangements by denaturing gradient gel electrophoresis of GC-clamped polymerase chain reaction products. Correlation with tumor-specific sequences. Am J Pathol 146:46–55PubMedGoogle Scholar
  28. 28.
    Groux H (2003) Type 1 T-regulatory cells: their role in the control of immune responses. Transplantation 75:8S–12SPubMedCrossRefGoogle Scholar
  29. 29.
    Harley CB (2008) Telomerase and cancer therapeutics. Nat Rev Cancer 8(3):167–179Google Scholar
  30. 30.
    Heiser A, Coleman D, Dannull J, Yancey D, Maurice MA, Lallas CD, Dahm P, Niedzwiecki D, Gilboa E, Vieweg J (2002) Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors. J Clin Invest 109:409–417PubMedGoogle Scholar
  31. 31.
    Hirschowitz EA, Foody T, Kryscio R, Dickson L, Sturgill J, Yannelli J (2004) Autologous dendritic cell vaccines for non-small-cell lung cancer. J Clin Oncol 22:2808–2815PubMedCrossRefGoogle Scholar
  32. 32.
    Hoos A, Parmiani G, Hege K, Sznol M, Loibner H, Eggermont A, Urba W, Blumenstein B, Sacks N, Keilholz U, Nichol G (2007) A clinical development paradigm for cancer vaccines and related biologics. J Immunother 30:1–15PubMedCrossRefGoogle Scholar
  33. 33.
    Janssen EM, Lemmens EE, Wolfe T, Christen U, von Herrath MG, Schoenberger SP (2003) CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature 421:852–856PubMedCrossRefGoogle Scholar
  34. 34.
    Kannanganat S, Ibegbu C, Chennareddi L, Robinson HL, Amara RR (2007) Multiple-cytokine-producing antiviral CD4 T cells are functionally superior to single-cytokine-producing cells. J Virol 81:8468–8476PubMedCrossRefGoogle Scholar
  35. 35.
    Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015PubMedCrossRefGoogle Scholar
  36. 36.
    Knutson KL, Disis ML (2005) Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother 54:721–728PubMedCrossRefGoogle Scholar
  37. 37.
    Kollgaard T, Petersen SL, Hadrup SR, Masmas TN, Seremet T, Andersen MH, Madsen HO, Vindelov L, thor Straten P (2005) Evidence for involvement of clonally expanded CD8+ T cells in anticancer immune responses in CLL patients following nonmyeloablative conditioning and hematopoietic cell transplantation. Leukemia 19:2273–2280PubMedCrossRefGoogle Scholar
  38. 38.
    Kotter I, Wacker A, Koch S, Henes J, Richter C, Engel A, Gunaydin I, Kanz L (2007) Anakinra in patients with treatment-resistant adult-onset Still’s disease: four case reports with serial cytokine measurements and a review of the literature. Semin Arthr Rheumat 37:189–197CrossRefGoogle Scholar
  39. 39.
    Kyte JA, Kvalheim G, Aamdal S, Saebøe-Larssen S, Gaudernack G (2005) Preclinical full-scale evaluation of dendritic cells transfected with autologous tumor-mRNA for melanoma vaccination. Cancer Gene Ther 12:579–591PubMedCrossRefGoogle Scholar
  40. 40.
    Kyte JA, Mu LJ, Aamdal S, Kvalheim G, Dueland S, Hauser M, Gullestad HP, Ryder T, Lislerud K, Hammerstad H, Gaudernack G (2006) Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA. Cancer Gene Ther 13:905–918PubMedCrossRefGoogle Scholar
  41. 41.
    Kyte JA, Kvalheim G, Lislerud K, Thor Straten P, Dueland S, Aamdal S, Gaudernack G (2007) T cell responses in melanoma patients after vaccination with tumor-mRNA transfected dendritic cells. Cancer Immunol Immunother 56:659–675PubMedCrossRefGoogle Scholar
  42. 42.
    Levings MK, Roncarolo MG (2005) Phenotypic and functional differences between human CD4+ CD25+ and type 1 regulatory T cells. Curr Top Microbiol Immunol 293:303–326PubMedCrossRefGoogle Scholar
  43. 43.
    Markowitz S, Wang J, Myeroff L, Parsons R, Sun L, Lutterbaugh J, Fan RS, Zborowska E, Kinzler KW, Vogelstein B et al (1995) Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 268:1336–1338PubMedCrossRefGoogle Scholar
  44. 44.
    Morse MA, Chui S, Hobeika A, Lyerly HK, Clay T (2005) Recent developments in therapeutic cancer vaccines. Nat Clin Prac 2:108–113CrossRefGoogle Scholar
  45. 45.
    Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357PubMedGoogle Scholar
  46. 46.
    Mosmann TR, Sad S (1996) The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17:138–146PubMedCrossRefGoogle Scholar
  47. 47.
    Myers RM, Maniatis T, Lerman LS (1987) Detection and localization of single base changes by denaturing gradient gel electrophoresis. Methods Enzymol 155:501–527PubMedCrossRefGoogle Scholar
  48. 48.
    Nagorsen D, Thiel E (2006) Clinical and immunologic responses to active specific cancer vaccines in human colorectal cancer. Clin Cancer Res 12:3064–3069PubMedCrossRefGoogle Scholar
  49. 49.
    Perambakam S, Hallmeyer S, Reddy S, Mahmud N, Bressler L, DeChristopher P, Mahmud D, Nunez R, Sosman JA, Peace DJ (2006) Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146–154 peptide. Cancer Immunol Immunother 55:1033–1042PubMedCrossRefGoogle Scholar
  50. 50.
    Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65:5506–5511PubMedCrossRefGoogle Scholar
  51. 51.
    Ridgway D (2003) The first 1000 dendritic cell vaccinees. Cancer Invest 21:873–886PubMedCrossRefGoogle Scholar
  52. 52.
    Rollins BJ (1997) Chemokines. Blood 90:909–928PubMedGoogle Scholar
  53. 53.
    Romagnani S (2008) Human Th17 cells. Arthr Res Ther 10:206–213CrossRefGoogle Scholar
  54. 54.
    Rosenberg SA, Yang JC, Restifo NP (2004) Cancer immunotherapy: moving beyond current vaccines. Nat Med 10:909–915PubMedCrossRefGoogle Scholar
  55. 55.
    Saeterdal I, Gjertsen MK, Straten P, Eriksen JA, Gaudernack G (2001) A TGF betaRII frameshift-mutation-derived CTL epitope recognised by HLA-A2-restricted CD8+ T cells. Cancer Immunol Immunother 50:469–476PubMedCrossRefGoogle Scholar
  56. 56.
    Salcedo M, Bercovici N, Taylor R, Vereecken P, Massicard S, Duriau D, Vernel-Pauillac F, Boyer A, Baron-Bodo V, Mallard E, Bartholeyns J, Goxe B, Latour N, Leroy S, Prigent D, Martiat P, Sales F, Laporte M, Bruyns C, Romet-Lemonne JL, Abastado JP, Lehmann F, Velu T (2006) Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate. Cancer Immunol Immunother 55:819–829PubMedCrossRefGoogle Scholar
  57. 57.
    Schuler-Thurner B, Schultz ES, Berger TG, Weinlich G, Ebner S, Woerl P, Bender A, Feuerstein B, Fritsch PO, Romani N, Schuler G (2002) Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med 195:1279–1288PubMedCrossRefGoogle Scholar
  58. 58.
    Shedlock DJ, Shen H (2003) Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 300:337–339PubMedCrossRefGoogle Scholar
  59. 59.
    Slingluff CL Jr, Yamshchikov G, Neese P, Galavotti H, Eastham S, Engelhard VH, Kittlesen D, Deacon D, Hibbitts S, Grosh WW, Petroni G, Cohen R, Wiernasz C, Patterson JW, Conway BP, Ross WG (2001) Phase I trial of a melanoma vaccine with gp100(280–288) peptide and tetanus helper peptide in adjuvant: immunologic and clinical outcomes. Clin Cancer Res 7:3012–3024PubMedGoogle Scholar
  60. 60.
    Strauss L, Bergmann C, Szczepanski M, Gooding W, Johnson JT, Whiteside TL (2007) A unique subset of CD4+ CD25highFoxp3+ T cells secreting interleukin-10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment. Clin Cancer Res 13:4345–4354PubMedCrossRefGoogle Scholar
  61. 61.
    Su Z, Dannull J, Heiser A, Yancey D, Pruitt S, Madden J, Coleman D, Niedzwiecki D, Gilboa E, Vieweg J (2003) Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. Cancer Res 63:2127–2133PubMedGoogle Scholar
  62. 62.
    thor Straten P, Barfoed A, Seremet T, Saeterdal I, Zeuthen J, Guldberg P (1998) Detection and characterization of alpha-beta-T-cell clonality by denaturing gradient gel electrophoresis (DGGE). Biotechniques 25:244–250PubMedGoogle Scholar
  63. 63.
    Toubaji A, Achtar M, Provenzano M, Herrin VE, Behrens R, Hamilton M, Bernstein S, Venzon D, Gause B, Marincola F, Khleif SN (2008) Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers. Cancer Immunol Immunother 57:1413–1420PubMedCrossRefGoogle Scholar
  64. 64.
    van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, Delabesse E, Davi F, Schuuring E, Garcia-Sanz R, van Krieken JH, Droese J, Gonzalez D, Bastard C, White HE, Spaargaren M, Gonzalez M, Parreira A, Smith JL, Morgan GJ, Kneba M, Macintyre EA (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 17:2257–2317PubMedCrossRefGoogle Scholar
  65. 65.
    Vence L, Palucka AK, Fay JW, Ito T, Liu YJ, Banchereau J, Ueno H (2007) Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma. Proc Natl Acad Sci USA 104:20884–20889PubMedCrossRefGoogle Scholar
  66. 66.
    Vonderheide RH (2002) Telomerase as a universal tumor-associated antigen for cancer immunotherapy. Oncogene 21:674–679PubMedCrossRefGoogle Scholar
  67. 67.
    Waldmann TA (2006) The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol 6:595–601PubMedCrossRefGoogle Scholar
  68. 68.
    Welsch T, Kleeff J, Friess H (2007) Molecular pathogenesis of pancreatic cancer: advances and challenges. Curr Mol Med 7:504–521PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Jon Amund Kyte
    • 1
    • 2
    Email author
  • Sissel Trachsel
    • 1
  • Bente Risberg
    • 3
  • Per thor Straten
    • 4
  • Kari Lislerud
    • 1
  • Gustav Gaudernack
    • 1
  1. 1.Section for Immunotherapy, Department of Immunology, Cancer Research InstituteThe Norwegian Radium Hospital, Rikshospitalet University Hospital, Medical Faculty, University of OsloOsloNorway
  2. 2.Department of Clinical Cancer ResearchThe Norwegian Radium HospitalOsloNorway
  3. 3.Department of PathologyThe Norwegian Radium HospitalOsloNorway
  4. 4.Department of Hematology, Center for Cancer Immune TherapyHerlev University HospitalHerlevDenmark

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