title: T cell responses in early-stage melanoma patients occur frequently and are not associated with humoral response.
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.
authors.affiliation: Division of Translational Immunology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.|Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Pfirschke
authors.affiliation: Skin Cancer Unit, DKFZ, Heidelberg, Germany.|Department of Dermatology, Ruperto-Carola University of Heidelberg, Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruperto-Carola University of Heidelberg, Mannheim, Germany.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Gebhardt
authors.affiliation: Department of Medical Oncology, NCT, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Inka
authors.initials: I
authors.lastname: Zörnig
authors.affiliation: Division of Translational Immunology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Pritsch
authors.affiliation: Division of Translational Immunology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
authors.forename: Stefan B
authors.initials: SB
authors.lastname: Eichmüller
authors.affiliation: Department of Medical Oncology, NCT, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.affiliation: Department of Dermatology, Ruperto-Carola University of Heidelberg, Heidelberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Enk
authors.affiliation: Division of Translational Immunology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. Philipp.Beckhove@klinik.uni-regensburg.de.|Regensburg Center for Interventional Immunology (RCI), University of Regensburg, Regensburg, Germany. Philipp.Beckhove@klinik.uni-regensburg.de.|University Clinic of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany. Philipp.Beckhove@klinik.uni-regensburg.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Beckhove
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology*; D006801:Humans; D058965:MART-1 Antigen / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000276:immunology; D009367:Neoplasm Staging; D013601:T-Lymphocytes / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C548667:MLANA protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D014442:Monophenol Monooxygenase
keywords: Autoantibodies; Malignant melanoma; Memory T cells; Regulatory T cells