Skip to main content

Advertisement

Springer Nature Link
Log in

T cell responses in early-stage melanoma patients occur frequently and are not associated with humoral response

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Endogenous tumor-specific T cells are detectable in patients with different tumor types including malignant melanoma (MM). They can control tumor growth, have impact on patient survival and correlate with improved clinical response to immune checkpoint therapy. Thus, they may represent a potent biomarker for respective treatment decisions. So far, major target antigens of endogenous MM-reactive T cells have not been determined systematically. Instead, autoantibodies are discussed as surrogate parameter for MM-specific T cells. Throughout a period of more than 60 days after tumor resection, we therefore determined in 38 non-metastasized primary MM patients and in healthy individuals by IFNγ ELISpot and bead-based fluorescent multiplex assay major target antigens of spontaneous T cell and humoral responses using a broad panel of MM antigens and assessed the presence and suppressive impact of MM-reactive regulatory T cells (Tregs). We show that MM-reactive T cells are frequent in MM patients, transiently increase after tumor removal and are mostly directed against Melan-A/MART-1, Tyrosinase, NA17-A and p53. MM-specific Tregs were only detected in few patients and inhibited MM-reactive T cells particularly early after tumor resection. Tumor-specific autoantibodies occurred in most patients, but did not correlate with T cell responses. Thus, endogenous antibodies may not be reliable surrogate parameters of MM-reactive T cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

DC:

Dendritic cell

HD:

Healthy donor

MM:

Malignant melanoma

PB:

Peripheral blood

PBMC:

Peripheral blood mononuclear cells

TAA:

Tumor-associated antigen

TC:

T cell

Tcon:

Conventional T cell

TCR:

T cell receptor

TIL:

Tumor-infiltrating lymphocyte

Treg:

Regulatory T cell

References

  1. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313(5795):1960–1964. doi:10.1126/science.1129139

    Article  CAS  PubMed  Google Scholar 

  2. Halama N, Michel S, Kloor M, Zoernig I, Benner A, Spille A, Pommerencke T, von Knebel DM, Folprecht G, Luber B, Feyen N, Martens UM, Beckhove P, Gnjatic S, Schirmacher P, Herpel E, Weitz J, Grabe N, Jaeger D (2011) Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res 71(17):5670–5677. doi:10.1158/0008-5472.CAN-11-0268

    Article  CAS  PubMed  Google Scholar 

  3. Al-Shibli KI, Donnem T, Al-Saad S, Persson M, Bremnes RM, Busund LT (2008) Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res 14(16):5220–5227. doi:10.1158/1078-0432.CCR-08-0133

    Article  CAS  PubMed  Google Scholar 

  4. Fukunaga A, Miyamoto M, Cho Y, Murakami S, Kawarada Y, Oshikiri T, Kato K, Kurokawa T, Suzuoki M, Nakakubo Y, Hiraoka K, Itoh T, Morikawa T, Okushiba S, Kondo S, Katoh H (2004) CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas 28(1):e26–e31

    Article  PubMed  Google Scholar 

  5. Lee PP, Yee C, Savage PA, Fong L, Brockstedt D, Weber JS, Johnson D, Swetter S, Thompson J, Greenberg PD, Roederer M, Davis MM (1999) Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat Med 5(6):677–685. doi:10.1038/9525

    Article  CAS  PubMed  Google Scholar 

  6. Inokuma M, de la Rosa C, Schmitt C, Haaland P, Siebert J, Petry D, Tang M, Suni MA, Ghanekar SA, Gladding D, Dunne JF, Maino VC, Disis ML, Maecker HT (2007) Functional T cell responses to tumor antigens in breast cancer patients have a distinct phenotype and cytokine signature. J Immunol 179(4):2627–2633

    Article  CAS  PubMed  Google Scholar 

  7. Choi C, Witzens M, Bucur M, Feuerer M, Sommerfeldt N, Trojan A, Ho A, Schirrmacher V, Goldschmidt H, Beckhove P (2005) Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma. Blood 105(5):2132–2134. doi:10.1182/blood-2004-01-0366

    Article  CAS  PubMed  Google Scholar 

  8. Schmitz-Winnenthal FH, Volk C, Z’Graggen K, Galindo L, Nummer D, Ziouta Y, Bucur M, Weitz J, Schirrmacher V, Buchler MW, Beckhove P (2005) High frequencies of functional tumor-reactive T cells in bone marrow and blood of pancreatic cancer patients. Cancer Res 65(21):10079–10087. doi:10.1158/0008-5472.CAN-05-1098

    Article  CAS  PubMed  Google Scholar 

  9. Muller-Berghaus J, Ehlert K, Ugurel S, Umansky V, Bucur M, Schirrmacher V, Beckhove P, Schadendorf D (2006) Melanoma-reactive T cells in the bone marrow of melanoma patients: association with disease stage and disease duration. Cancer Res 66(12):5997–6001. doi:10.1158/0008-5472.CAN-04-0484

    Article  PubMed  Google Scholar 

  10. Sommerfeldt N, Beckhove P, Ge Y, Schutz F, Choi C, Bucur M, Domschke C, Sohn C, Schneeweis A, Rom J, Pollmann D, Leucht D, Vlodavsky I, Schirrmacher V (2006) Heparanase: a new metastasis-associated antigen recognized in breast cancer patients by spontaneously induced memory T lymphocytes. Cancer Res 66(15):7716–7723. doi:10.1158/0008-5472.CAN-05-2363

    Article  CAS  PubMed  Google Scholar 

  11. Sommerfeldt N, Schutz F, Sohn C, Forster J, Schirrmacher V, Beckhove P (2006) The shaping of a polyvalent and highly individual T-cell repertoire in the bone marrow of breast cancer patients. Cancer Res 66(16):8258–8265. doi:10.1158/0008-5472.CAN-05-4201

    Article  CAS  PubMed  Google Scholar 

  12. Bonertz A, Weitz J, Pietsch DH, Rahbari NN, Schlude C, Ge Y, Juenger S, Vlodavsky I, Khazaie K, Jaeger D, Reissfelder C, Antolovic D, Aigner M, Koch M, Beckhove P (2009) Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma. J Clin Invest 119(11):3311–3321. doi:10.1172/JCI39608

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Horn T, Grab J, Schusdziarra J, Schmid S, Maurer T, Nawroth R, Wolf P, Pritsch M, Gschwend JE, Kubler HR, Beckhove P (2013) Antitumor T cell responses in bladder cancer are directed against a limited set of antigens and are modulated by regulatory T cells and routine treatment approaches. Int J Cancer 133(9):2145–2156. doi:10.1002/ijc.28233

    Article  CAS  PubMed  Google Scholar 

  14. Rosenberg SA, Restifo NP (2015) Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348(6230):62–68. doi:10.1126/science.aaa4967

    Article  CAS  PubMed  Google Scholar 

  15. Beckhove P, Feuerer M, Dolenc M, Schuetz F, Choi C, Sommerfeldt N, Schwendemann J, Ehlert K, Altevogt P, Bastert G, Schirrmacher V, Umansky V (2004) Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors. J Clin Invest 114(1):67–76. doi:10.1172/JCI20278

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Stroncek DF, Berger C, Cheever MA, Childs RW, Dudley ME, Flynn P, Gattinoni L, Heath JR, Kalos M, Marincola FM, Miller JS, Mostoslavsky G, Powell DJ Jr, Rao M, Restifo NP, Rosenberg SA, O’Shea J, Melief CJ (2012) New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer. J Transl Med 10:48. doi:10.1186/1479-5876-10-48

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Feuerer M, Beckhove P, Bai L, Solomayer EF, Bastert G, Diel IJ, Pedain C, Oberniedermayr M, Schirrmacher V, Umansky V (2001) Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow. Nat Med 7(4):452–458. doi:10.1038/86523

    Article  CAS  PubMed  Google Scholar 

  18. Domschke C, Ge Y, Bernhardt I, Schott S, Keim S, Juenger S, Bucur M, Mayer L, Blumenstein M, Rom J, Heil J, Sohn C, Schneeweiss A, Beckhove P, Schuetz F (2013) Long-term survival after adoptive bone marrow T cell therapy of advanced metastasized breast cancer: follow-up analysis of a clinical pilot trial. Cancer Immunol Immunother 62(6):1053–1060. doi:10.1007/s00262-013-1414-x

    Article  CAS  PubMed  Google Scholar 

  19. Dudley ME, Gross CA, Langhan MM, Garcia MR, Sherry RM, Yang JC, Phan GQ, Kammula US, Hughes MS, Citrin DE, Restifo NP, Wunderlich JR, Prieto PA, Hong JJ, Langan RC, Zlott DA, Morton KE, White DE, Laurencot CM, Rosenberg SA (2010) CD8+ enriched “young” tumor infiltrating lymphocytes can mediate regression of metastatic melanoma. Clin Cancer Res 16(24):6122–6131. doi:10.1158/1078-0432.CCR-10-1297

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Sharma P, Allison JP (2015) The future of immune checkpoint therapy. Science 348(6230):56–61. doi:10.1126/science.aaa8172

    Article  CAS  PubMed  Google Scholar 

  21. Yuan J, Gnjatic S, Li H, Powel S, Gallardo HF, Ritter E, Ku GY, Jungbluth AA, Segal NH, Rasalan TS, Manukian G, Xu Y, Roman RA, Terzulli SL, Heywood M, Pogoriler E, Ritter G, Old LJ, Allison JP, Wolchok JD (2008) CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit. Proc Natl Acad Sci USA 105(51):20410–20415. doi:10.1073/pnas.0810114105

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Griewank KG, Ugurel S, Schadendorf D, Paschen A (2013) New developments in biomarkers for melanoma. Curr Opin Oncol 25(2):145–151. doi:10.1097/CCO.0b013e32835dafdf

    Article  CAS  PubMed  Google Scholar 

  23. Andersen RS, Thrue CA, Junker N, Lyngaa R, Donia M, Ellebaek E, Svane IM, Schumacher TN, Thor Straten P, Hadrup SR (2012) Dissection of T-cell antigen specificity in human melanoma. Cancer Res 72(7):1642–1650. doi:10.1158/0008-5472.CAN-11-2614

    Article  CAS  PubMed  Google Scholar 

  24. Slingluff CL Jr (2011) The present and future of peptide vaccines for cancer: single or multiple, long or short, alone or in combination? Cancer J 17(5):343–350. doi:10.1097/PPO.0b013e318233e5b2

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Mourmouras V, Fimiani M, Rubegni P, Epistolato MC, Malagnino V, Cardone C, Cosci E, Nisi MC, Miracco C (2007) Evaluation of tumour-infiltrating CD4+ CD25+ FOXP3+ regulatory T cells in human cutaneous benign and atypical naevi, melanomas and melanoma metastases. Br J Dermatol 157(3):531–539. doi:10.1111/j.1365-2133.2007.08057.x

    Article  CAS  PubMed  Google Scholar 

  26. Whiteside TL (2014) Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression? Cancer Immunol Immunother 63(1):67–72. doi:10.1007/s00262-013-1490-y

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Ge Y, Domschke C, Stoiber N, Schott S, Heil J, Rom J, Blumenstein M, Thum J, Sohn C, Schneeweiss A, Beckhove P, Schuetz F (2012) Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome. Cancer Immunol Immunother 61(3):353–362. doi:10.1007/s00262-011-1106-3

    Article  CAS  PubMed  Google Scholar 

  28. Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B (2007) Metronomic cyclophosphamide regimen selectively depletes CD4+ CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 56(5):641–648. doi:10.1007/s00262-006-0225-8

    Article  CAS  PubMed  Google Scholar 

  29. Gnjatic S, Ritter E, Buchler MW, Giese NA, Brors B, Frei C, Murray A, Halama N, Zornig I, Chen YT, Andrews C, Ritter G, Old LJ, Odunsi K, Jager D (2010) Seromic profiling of ovarian and pancreatic cancer. Proc Natl Acad Sci USA 107(11):5088–5093. doi:10.1073/pnas.0914213107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Sangrajrang S, Arpornwirat W, Cheirsilpa A, Thisuphakorn P, Kalalak A, Sornprom A, Soussi T (2003) Serum p53 antibodies in correlation to other biological parameters of breast cancer. Cancer Detect Prev 27(3):182–186

    Article  CAS  PubMed  Google Scholar 

  31. Taylor DD, Gercel-Taylor C, Parker LP (2009) Patient-derived tumor-reactive antibodies as diagnostic markers for ovarian cancer. Gynecol Oncol 115(1):112–120. doi:10.1016/j.ygyno.2009.06.031

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Zhang Y, Ying X, Han S, Wang J, Zhou X, Bai E, Zhang J, Zhu Q (2013) Autoantibodies against insulin-like growth factorbinding protein-2 as a serological biomarker in the diagnosis of lung cancer. Int J Oncol 42(1):93–100. doi:10.3892/ijo.2012.1699

    PubMed Central  PubMed  Google Scholar 

  33. Gogas H, Ioannovich J, Dafni U, Stavropoulou-Giokas C, Frangia K, Tsoutsos D, Panagiotou P, Polyzos A, Papadopoulos O, Stratigos A, Markopoulos C, Bafaloukos D, Pectasides D, Fountzilas G, Kirkwood JM (2006) Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med 354(7):709–718. doi:10.1056/NEJMoa053007

    Article  CAS  PubMed  Google Scholar 

  34. Schoenfeld J, Jinushi M, Nakazaki Y, Wiener D, Park J, Soiffer R, Neuberg D, Mihm M, Hodi FS, Dranoff G (2010) Active immunotherapy induces antibody responses that target tumor angiogenesis. Cancer Res 70(24):10150–10160. doi:10.1158/0008-5472.CAN-10-1852

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Mahnke YD, Schwendemann J, Beckhove P, Schirrmacher V (2005) Maintenance of long-term tumour-specific T-cell memory by residual dormant tumour cells. Immunology 115(3):325–336. doi:10.1111/j.1365-2567.2005.02163.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Lennerz V, Fatho M, Gentilini C, Frye RA, Lifke A, Ferel D, Wolfel C, Huber C, Wolfel T (2005) The response of autologous T cells to a human melanoma is dominated by mutated neoantigens. Proc Natl Acad Sci USA 102(44):16013–16018. doi:10.1073/pnas.0500090102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Kvistborg P, Shu CJ, Heemskerk B, Fankhauser M, Thrue CA, Toebes M, van Rooij N, Linnemann C, van Buuren MM, Urbanus JH, Beltman JB, Thor Straten P, Li YF, Robbins PF, Besser MJ, Schachter J, Kenter GG, Dudley ME, Rosenberg SA, Haanen JB, Hadrup SR, Schumacher TN (2012) TIL therapy broadens the tumor-reactive CD8(+) T cell compartment in melanoma patients. Oncoimmunology 1(4):409–418

    Article  PubMed Central  PubMed  Google Scholar 

  38. Andersen RS, Andersen SR, Hjortso MD, Lyngaa R, Idorn M, Kollgard TM, Met O, Thor Straten P, Hadrup SR (2013) High frequency of T cells specific for cryptic epitopes in melanoma patients. Oncoimmunology 2(7):e25374. doi:10.4161/onci.25374

    Article  PubMed Central  PubMed  Google Scholar 

  39. Schumacher TN, Schreiber RD (2015) Neoantigens in cancer immunotherapy. Science 348(6230):69–74. doi:10.1126/science.aaa4971

    Article  CAS  PubMed  Google Scholar 

  40. Weide B, Zelba H, Derhovanessian E, Pflugfelder A, Eigentler TK, Di Giacomo AM, Maio M, Aarntzen EH, de Vries IJ, Sucker A, Schadendorf D, Buttner P, Garbe C, Pawelec G (2012) Functional T cells targeting NY-ESO-1 or Melan-A are predictive for survival of patients with distant melanoma metastasis. J Clin Oncol 30(15):1835–1841. doi:10.1200/JCO.2011.40.2271

    Article  CAS  PubMed  Google Scholar 

  41. Reissfelder C, Stamova S, Gossmann C, Braun M, Bonertz A, Walliczek U, Grimm M, Rahbari NN, Koch M, Saadati M, Benner A, Buchler MW, Jager D, Halama N, Khazaie K, Weitz J, Beckhove P (2015) Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis. J Clin Invest 125(2):739–751. doi:10.1172/JCI74894

    Article  PubMed Central  PubMed  Google Scholar 

  42. Guilloux Y, Lucas S, Brichard VG, Van Pel A, Viret C, De Plaen E, Brasseur F, Lethe B, Jotereau F, Boon T (1996) A peptide recognized by human cytolytic T lymphocytes on HLA-A2 melanomas is encoded by an intron sequence of the N-acetylglucosaminyltransferase V gene. J Exp Med 183(3):1173–1183

    Article  CAS  PubMed  Google Scholar 

  43. Waterboer T, Sehr P, Michael KM, Franceschi S, Nieland JD, Joos TO, Templin MF, Pawlita M (2005) Multiplex human papillomavirus serology based on in situ-purified glutathione s-transferase fusion proteins. Clin Chem 51(10):1845–1853. doi:10.1373/clinchem.2005.052381

    Article  CAS  PubMed  Google Scholar 

  44. Dummer R, Eichmuller S, Gellrich S, Assaf C, Dreno B, Schiller M, Dereure O, Baudard M, Bagot M, Khammari A, Bleuzen P, Bataille V, Derbij A, Wiedemann N, Waterboer T, Lusky M, Acres B, Urosevic-Maiwald M (2010) Phase II clinical trial of intratumoral application of TG1042 (adenovirus-interferon-gamma) in patients with advanced cutaneous T-cell lymphomas and multilesional cutaneous B-cell lymphomas. Mol Ther 18(6):1244–1247. doi:10.1038/mt.2010.52

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Zornig I, Halama N, Lorenzo Bermejo J, Ziegelmeier C, Dickes E, Migdoll A, Kaiser I, Waterboer T, Pawlita M, Grabe N, Ugurel S, Schadendorf D, Falk C, Eichmuller SB, Jager D (2015) Prognostic significance of spontaneous antibody responses against tumor-associated antigens in malignant melanoma patients. Int J Cancer 136(1):138–151. doi:10.1002/ijc.28980

    Article  PubMed  Google Scholar 

  46. Moodie Z, Price L, Gouttefangeas C, Mander A, Janetzki S, Lower M, Welters MJ, Ottensmeier C, van der Burg SH, Britten CM (2010) Response definition criteria for ELISPOT assays revisited. Cancer Immunol Immunother 59(10):1489–1501. doi:10.1007/s00262-010-0875-4

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Melief CJ, van der Burg SH (2008) Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nat Rev Cancer 8(5):351–360. doi:10.1038/nrc2373

    Article  CAS  PubMed  Google Scholar 

  48. Aranda F, Vacchelli E, Eggermont A, Galon J, Sautes-Fridman C, Tartour E, Zitvogel L, Kroemer G, Galluzzi L (2013) Trial Watch: peptide vaccines in cancer therapy. Oncoimmunology 2(12):e26621. doi:10.4161/onci.26621

    Article  PubMed Central  PubMed  Google Scholar 

  49. McCarter MD, Baumgartner J, Escobar GA, Richter D, Lewis K, Robinson W, Wilson C, Palmer BE, Gonzalez R (2007) Immunosuppressive dendritic and regulatory T cells are upregulated in melanoma patients. Ann Surg Oncol 14(10):2854–2860. doi:10.1245/s10434-007-9488-3

    Article  PubMed  Google Scholar 

  50. Mocellin S, Hoon D, Ambrosi A, Nitti D, Rossi CR (2006) The prognostic value of circulating tumor cells in patients with melanoma: a systematic review and meta-analysis. Clin Cancer Res 12(15):4605–4613. doi:10.1158/1078-0432.CCR-06-0823

    Article  CAS  PubMed  Google Scholar 

  51. Strauss DC, Thomas JM (2010) Transmission of donor melanoma by organ transplantation. Lancet Oncol 11(8):790–796. doi:10.1016/S1470-2045(10)70024-3

    Article  PubMed  Google Scholar 

  52. van der Burg SH, de Cock K, Menon AG, Franken KL, Palmen M, Redeker A, Drijfhout J, Kuppen PJ, van de Velde C, Erdile L, Tollenaar RA, Melief CJ, Offringa R (2001) Long lasting p53-specific T cell memory responses in the absence of anti-p53 antibodies in patients with resected primary colorectal cancer. Eur J Immunol 31(1):146–155. doi:10.1002/1521-4141(200101)31:1<146:AID-IMMU146>3.0.CO;2-T

    Article  PubMed  Google Scholar 

  53. Jager E, Chen YT, Drijfhout JW, Karbach J, Ringhoffer M, Jager D, Arand M, Wada H, Noguchi Y, Stockert E, Old LJ, Knuth A (1998) Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes. J Exp Med 187(2):265–270

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Gnjatic S, Atanackovic D, Jager E, Matsuo M, Selvakumar A, Altorki NK, Maki RG, Dupont B, Ritter G, Chen YT, Knuth A, Old LJ (2003) Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: correlation with antibody responses. Proc Natl Acad Sci USA 100(15):8862–8867. doi:10.1073/pnas.1133324100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Tilkin AF, Lubin R, Soussi T, Lazar V, Janin N, Mathieu MC, Lefrere I, Carlu C, Roy M, Kayibanda M et al (1995) Primary proliferative T cell response to wild-type p53 protein in patients with breast cancer. Eur J Immunol 25(6):1765–1769. doi:10.1002/eji.1830250642

    Article  CAS  PubMed  Google Scholar 

  56. Zalcman G, Schlichtholz B, Tredaniel J, Urban T, Lubin R, Dubois I, Milleron B, Hirsch A, Soussi T (1998) Monitoring of p53 autoantibodies in lung cancer during therapy: relationship to response to treatment. Clin Cancer Res 4(6):1359–1366

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Simone Jünger (Division of Translational Immunology, DKFZ) and Iris Kaiser (Department of Medical Oncology, NCT) for excellent technical assistance. Drs. Andreas Bonertz and Yingzi Ge (Division of Translational Immunology) for helpful discussions concerning the Treg specificity assay, Dr. Steffen Rickelt (Helmholtz Group for Cell Biology, DKFZ) for reading the manuscript and Dr. Michael Pawlita (Division of Genome Modifications and Carcinogenesis, DKFZ) for providing the recombinant p16 and p53 proteins used for the multiplex assay. This work was supported by the Initiative and Networking Fund of the Helmholtz Alliance on Immunotherapy of Cancer and by the Deutsche Forschungsgemeinschaft (DFG; SFB938).

Author information

Author notes

  1. Christina Pfirschke

    Present address: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

  2. Christoffer Gebhardt

    Present address: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruperto-Carola University of Heidelberg, Mannheim, Germany

  3. Philipp Beckhove

    Present address: Regensburg Center for Interventional Immunology (RCI), University of Regensburg, Regensburg, Germany

Authors and Affiliations

  1. Division of Translational Immunology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany

    Christina Pfirschke, Maria Pritsch, Stefan B. Eichmüller & Philipp Beckhove

  2. Skin Cancer Unit, DKFZ, Heidelberg, Germany

    Christoffer Gebhardt

  3. Department of Dermatology, Ruperto-Carola University of Heidelberg, Heidelberg, Germany

    Christoffer Gebhardt & Alexander Enk

  4. Department of Medical Oncology, NCT, Heidelberg University Hospital, Heidelberg, Germany

    Inka Zörnig & Dirk Jäger

  5. University Clinic of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

    Philipp Beckhove

Authors
  1. Christina Pfirschke
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Christoffer Gebhardt
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Inka Zörnig
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Maria Pritsch
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Stefan B. Eichmüller
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Dirk Jäger
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Alexander Enk
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Philipp Beckhove
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Philipp Beckhove.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 1008 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pfirschke, C., Gebhardt, C., Zörnig, I. et al. T cell responses in early-stage melanoma patients occur frequently and are not associated with humoral response. Cancer Immunol Immunother 64, 1369–1381 (2015). https://doi.org/10.1007/s00262-015-1739-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-015-1739-8

Keywords