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

TY - JOUR

T1 - T cell responses in early-stage melanoma patients occur frequently and are not associated with humoral response

AU - Pfirschke, Christina

AU - Gebhardt, Christoffer

AU - Zörnig, Inka

AU - Pritsch, Maria

AU - Eichmüller, Stefan B

AU - Jäger, Dirk

AU - Enk, Alexander

AU - Beckhove, Philipp

PY - 2015/11

Y1 - 2015/11

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Antigens, Neoplasm

KW - Humans

KW - MART-1 Antigen

KW - Melanoma

KW - Molecular Sequence Data

KW - Monophenol Monooxygenase

KW - Neoplasm Staging

KW - T-Lymphocytes

KW - Tumor Suppressor Protein p53

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1007/s00262-015-1739-8

DO - 10.1007/s00262-015-1739-8

M3 - SCORING: Journal article

C2 - 26160687

VL - 64

SP - 1369

EP - 1381

JO - CANCER IMMUNOL IMMUN

JF - CANCER IMMUNOL IMMUN

SN - 0340-7004

IS - 11

ER -