Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity

Marco Donia; Rikke Andersen; Julie W Kjeldsen; Paolo Fagone; Shamaila Munir; Ferdinando Nicoletti; Mads Hald Andersen; Per Thor Straten; Inge Marie Svane

doi:10.1158/0008-5472.can-14-2956

Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4⁺ T- Cells, Which Dampen CD8⁺ T-cell Antitumor Reactivity

Marco Donia, Rikke Andersen, Julie W Kjeldsen, Paolo Fagone, Shamaila Munir, Ferdinando Nicoletti, Mads Hald Andersen, Per Thor Straten, Inge Marie Svane

Institut for Klinisk Medicin

51 Citationer (Scopus)

Abstract

In the absence of a local inflammatory response, expression of MHC class II molecules is restricted mainly to hematopoietic cells and thymus epithelium. However, certain tumors, such as melanoma, may acquire aberrant constitutive expression of MHC class II. In a set of primary melanoma cell populations and correspondingly expanded autologous tumor-infiltrating lymphocytes (TIL), we show how MHC class II expression on melanoma cells associates with strong MHC class II-restricted CD4⁺T-cell responses that are specific for tumors. Notably, we found that tumor-specific CD4⁺T-cell responses were dominated by TNF production. TNF reduced CD8⁺T-cell activation in IFNγ-rich environments resembling a tumor site. Conversely, direct CD4⁺T-cell responses had no influence on either the proliferation or viability of melanoma cells.

Originalsprog	Engelsk
Tidsskrift	Cancer Research
Vol/bind	75
Udgave nummer	18
Sider (fra-til)	3747-59
Antal sider	13
ISSN	0008-5472
DOI	https://doi.org/10.1158/0008-5472.can-14-2956
Status	Udgivet - 15 sep. 2015

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10.1158/0008-5472.can-14-2956

3747.full.pdfForlagets udgivne version, 1,15 MB
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Citationsformater

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title = "Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity",

abstract = "In the absence of a local inflammatory response, expression of MHC class II molecules is restricted mainly to hematopoietic cells and thymus epithelium. However, certain tumors, such as melanoma, may acquire aberrant constitutive expression of MHC class II. In a set of primary melanoma cell populations and correspondingly expanded autologous tumor-infiltrating lymphocytes (TIL), we show how MHC class II expression on melanoma cells associates with strong MHC class II-restricted CD4+T-cell responses that are specific for tumors. Notably, we found that tumor-specific CD4+T-cell responses were dominated by TNF production. TNF reduced CD8+T-cell activation in IFNγ-rich environments resembling a tumor site. Conversely, direct CD4+T-cell responses had no influence on either the proliferation or viability of melanoma cells.",

keywords = "Antigens, Neoplasm, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Chemotaxis, Leukocyte, Coculture Techniques, Cytotoxicity, Immunologic, Gene Expression Regulation, Neoplastic, Genes, MHC Class II, HLA-D Antigens, Humans, Interferon-gamma Release Tests, Lymphocyte Activation, Lymphocytes, Tumor-Infiltrating, Melanoma, T-Lymphocyte Subsets",

author = "Marco Donia and Rikke Andersen and Kjeldsen, {Julie W} and Paolo Fagone and Shamaila Munir and Ferdinando Nicoletti and Andersen, {Mads Hald} and {Thor Straten}, Per and Svane, {Inge Marie}",

note = "{\textcopyright}2015 American Association for Cancer Research.",

year = "2015",

month = sep,

day = "15",

doi = "10.1158/0008-5472.can-14-2956",

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TY - JOUR

T1 - Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity

AU - Donia, Marco

AU - Andersen, Rikke

AU - Kjeldsen, Julie W

AU - Fagone, Paolo

AU - Munir, Shamaila

AU - Nicoletti, Ferdinando

AU - Andersen, Mads Hald

AU - Thor Straten, Per

AU - Svane, Inge Marie

PY - 2015/9/15

Y1 - 2015/9/15

N2 - In the absence of a local inflammatory response, expression of MHC class II molecules is restricted mainly to hematopoietic cells and thymus epithelium. However, certain tumors, such as melanoma, may acquire aberrant constitutive expression of MHC class II. In a set of primary melanoma cell populations and correspondingly expanded autologous tumor-infiltrating lymphocytes (TIL), we show how MHC class II expression on melanoma cells associates with strong MHC class II-restricted CD4+T-cell responses that are specific for tumors. Notably, we found that tumor-specific CD4+T-cell responses were dominated by TNF production. TNF reduced CD8+T-cell activation in IFNγ-rich environments resembling a tumor site. Conversely, direct CD4+T-cell responses had no influence on either the proliferation or viability of melanoma cells.

AB - In the absence of a local inflammatory response, expression of MHC class II molecules is restricted mainly to hematopoietic cells and thymus epithelium. However, certain tumors, such as melanoma, may acquire aberrant constitutive expression of MHC class II. In a set of primary melanoma cell populations and correspondingly expanded autologous tumor-infiltrating lymphocytes (TIL), we show how MHC class II expression on melanoma cells associates with strong MHC class II-restricted CD4+T-cell responses that are specific for tumors. Notably, we found that tumor-specific CD4+T-cell responses were dominated by TNF production. TNF reduced CD8+T-cell activation in IFNγ-rich environments resembling a tumor site. Conversely, direct CD4+T-cell responses had no influence on either the proliferation or viability of melanoma cells.

KW - Antigens, Neoplasm

KW - CD4-Positive T-Lymphocytes

KW - CD8-Positive T-Lymphocytes

KW - Cell Line, Tumor

KW - Chemotaxis, Leukocyte

KW - Coculture Techniques

KW - Cytotoxicity, Immunologic

KW - Gene Expression Regulation, Neoplastic

KW - Genes, MHC Class II

KW - HLA-D Antigens

KW - Humans

KW - Interferon-gamma Release Tests

KW - Lymphocyte Activation

KW - Lymphocytes, Tumor-Infiltrating

KW - Melanoma

KW - T-Lymphocyte Subsets

U2 - 10.1158/0008-5472.can-14-2956

DO - 10.1158/0008-5472.can-14-2956

M3 - Journal article

C2 - 26183926

SN - 0008-5472

VL - 75

SP - 3747

EP - 3759

JO - Cancer Research

JF - Cancer Research

IS - 18

ER -

Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity

Abstract

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Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4⁺ T- Cells, Which Dampen CD8⁺ T-cell Antitumor Reactivity