TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis

Nele Müller-Hermelink; Heidi Braumüller; Bernd Pichler; Thomas Wieder; Reinhard Mailhammer; Katrin Schaak; Kamran Ghoreschi; Amir Yazdi; Roland Haubner; Christian A Sander; Ralph Mocikat; Markus Schwaiger; Irmgard Förster; Ralph Huss; Wolfgang A Weber; Manfred Kneilling; Martin Röcken

doi:10.1016/j.ccr.2008.04.001

TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis

Nele Müller-Hermelink, Heidi Braumüller, Bernd Pichler, Thomas Wieder, Reinhard Mailhammer, Katrin Schaak, Kamran Ghoreschi, Amir Yazdi, Roland Haubner, Christian A Sander, Ralph Mocikat, Markus Schwaiger, Irmgard Förster, Ralph Huss, Wolfgang A Weber, Manfred Kneilling, Martin Röcken

Research output: Contribution to journal › Article › peer-review

Abstract

Immune responses may arrest tumor growth by inducing tumor dormancy. The mechanisms leading to either tumor dormancy or promotion of multistage carcinogenesis by adaptive immunity are poorly characterized. Analyzing T antigen (Tag)-induced multistage carcinogenesis in pancreatic islets, we show that Tag-specific CD4+ T cells home selectively into the tumor microenvironment around the islets, where they either arrest or promote transition of dysplastic islets into islet carcinomas. Through combined TNFR1 signaling and IFN-gamma signaling, Tag-specific CD4+ T cells induce antiangiogenic chemokines and prevent alpha(v)beta(3) integrin expression, tumor angiogenesis, tumor cell proliferation, and multistage carcinogenesis, without destroying Tag-expressing islet cells. In the absence of either TNFR1 signaling or IFN-gamma signaling, the same T cells paradoxically promote angiogenesis and multistage carcinogenesis. Thus, tumor-specific T cells can directly survey multistage carcinogenesis through cytokine signaling.

Original language	English
Pages (from-to)	507-18
Number of pages	12
Journal	Cancer Cell
Volume	13
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2008.04.001
Publication status	Published - Jun 2008

Keywords / Materials (for Non-textual outputs)

Animals
Antigens, Viral, Tumor
Blood Glucose
CD4-Positive T-Lymphocytes
Cell Movement
Cell Proliferation
Cell Survival
Cell Transformation, Neoplastic
Cells, Cultured
GTPase-Activating Proteins
Immunotherapy
Insulinoma
Integrin alphaVbeta3
Interferon-gamma
Mice
Mice, Inbred C3H
Mice, Knockout
Mice, Transgenic
Neovascularization, Pathologic
Pancreatic Neoplasms
Receptors, Tumor Necrosis Factor, Type I
Signal Transduction
Th1 Cells
Time Factors
Whole-Body Irradiation

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10.1016/j.ccr.2008.04.001

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Müller-Hermelink, N., Braumüller, H., Pichler, B., Wieder, T., Mailhammer, R., Schaak, K., Ghoreschi, K., Yazdi, A., Haubner, R., Sander, C. A., Mocikat, R., Schwaiger, M., Förster, I., Huss, R., Weber, W. A., Kneilling, M., & Röcken, M. (2008). TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis. Cancer Cell, 13(6), 507-18. https://doi.org/10.1016/j.ccr.2008.04.001

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title = "TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis",

abstract = "Immune responses may arrest tumor growth by inducing tumor dormancy. The mechanisms leading to either tumor dormancy or promotion of multistage carcinogenesis by adaptive immunity are poorly characterized. Analyzing T antigen (Tag)-induced multistage carcinogenesis in pancreatic islets, we show that Tag-specific CD4+ T cells home selectively into the tumor microenvironment around the islets, where they either arrest or promote transition of dysplastic islets into islet carcinomas. Through combined TNFR1 signaling and IFN-gamma signaling, Tag-specific CD4+ T cells induce antiangiogenic chemokines and prevent alpha(v)beta(3) integrin expression, tumor angiogenesis, tumor cell proliferation, and multistage carcinogenesis, without destroying Tag-expressing islet cells. In the absence of either TNFR1 signaling or IFN-gamma signaling, the same T cells paradoxically promote angiogenesis and multistage carcinogenesis. Thus, tumor-specific T cells can directly survey multistage carcinogenesis through cytokine signaling.",

keywords = "Animals, Antigens, Viral, Tumor, Blood Glucose, CD4-Positive T-Lymphocytes, Cell Movement, Cell Proliferation, Cell Survival, Cell Transformation, Neoplastic, Cells, Cultured, GTPase-Activating Proteins, Immunotherapy, Insulinoma, Integrin alphaVbeta3, Interferon-gamma, Mice, Mice, Inbred C3H, Mice, Knockout, Mice, Transgenic, Neovascularization, Pathologic, Pancreatic Neoplasms, Receptors, Tumor Necrosis Factor, Type I, Signal Transduction, Th1 Cells, Time Factors, Whole-Body Irradiation",

author = "Nele M{\"u}ller-Hermelink and Heidi Braum{\"u}ller and Bernd Pichler and Thomas Wieder and Reinhard Mailhammer and Katrin Schaak and Kamran Ghoreschi and Amir Yazdi and Roland Haubner and Sander, \{Christian A\} and Ralph Mocikat and Markus Schwaiger and Irmgard F{\"o}rster and Ralph Huss and Weber, \{Wolfgang A\} and Manfred Kneilling and Martin R{\"o}cken",

year = "2008",

month = jun,

doi = "10.1016/j.ccr.2008.04.001",

language = "English",

volume = "13",

pages = "507--18",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

}

Müller-Hermelink, N, Braumüller, H, Pichler, B, Wieder, T, Mailhammer, R, Schaak, K, Ghoreschi, K, Yazdi, A, Haubner, R, Sander, CA, Mocikat, R, Schwaiger, M, Förster, I, Huss, R, Weber, WA, Kneilling, M & Röcken, M 2008, 'TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis', Cancer Cell, vol. 13, no. 6, pp. 507-18. https://doi.org/10.1016/j.ccr.2008.04.001

TY - JOUR

T1 - TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis

AU - Müller-Hermelink, Nele

AU - Braumüller, Heidi

AU - Pichler, Bernd

AU - Wieder, Thomas

AU - Mailhammer, Reinhard

AU - Schaak, Katrin

AU - Ghoreschi, Kamran

AU - Yazdi, Amir

AU - Haubner, Roland

AU - Sander, Christian A

AU - Mocikat, Ralph

AU - Schwaiger, Markus

AU - Förster, Irmgard

AU - Huss, Ralph

AU - Weber, Wolfgang A

AU - Kneilling, Manfred

AU - Röcken, Martin

PY - 2008/6

Y1 - 2008/6

N2 - Immune responses may arrest tumor growth by inducing tumor dormancy. The mechanisms leading to either tumor dormancy or promotion of multistage carcinogenesis by adaptive immunity are poorly characterized. Analyzing T antigen (Tag)-induced multistage carcinogenesis in pancreatic islets, we show that Tag-specific CD4+ T cells home selectively into the tumor microenvironment around the islets, where they either arrest or promote transition of dysplastic islets into islet carcinomas. Through combined TNFR1 signaling and IFN-gamma signaling, Tag-specific CD4+ T cells induce antiangiogenic chemokines and prevent alpha(v)beta(3) integrin expression, tumor angiogenesis, tumor cell proliferation, and multistage carcinogenesis, without destroying Tag-expressing islet cells. In the absence of either TNFR1 signaling or IFN-gamma signaling, the same T cells paradoxically promote angiogenesis and multistage carcinogenesis. Thus, tumor-specific T cells can directly survey multistage carcinogenesis through cytokine signaling.

AB - Immune responses may arrest tumor growth by inducing tumor dormancy. The mechanisms leading to either tumor dormancy or promotion of multistage carcinogenesis by adaptive immunity are poorly characterized. Analyzing T antigen (Tag)-induced multistage carcinogenesis in pancreatic islets, we show that Tag-specific CD4+ T cells home selectively into the tumor microenvironment around the islets, where they either arrest or promote transition of dysplastic islets into islet carcinomas. Through combined TNFR1 signaling and IFN-gamma signaling, Tag-specific CD4+ T cells induce antiangiogenic chemokines and prevent alpha(v)beta(3) integrin expression, tumor angiogenesis, tumor cell proliferation, and multistage carcinogenesis, without destroying Tag-expressing islet cells. In the absence of either TNFR1 signaling or IFN-gamma signaling, the same T cells paradoxically promote angiogenesis and multistage carcinogenesis. Thus, tumor-specific T cells can directly survey multistage carcinogenesis through cytokine signaling.

KW - Animals

KW - Antigens, Viral, Tumor

KW - Blood Glucose

KW - CD4-Positive T-Lymphocytes

KW - Cell Movement

KW - Cell Proliferation

KW - Cell Survival

KW - Cell Transformation, Neoplastic

KW - Cells, Cultured

KW - GTPase-Activating Proteins

KW - Immunotherapy

KW - Insulinoma

KW - Integrin alphaVbeta3

KW - Interferon-gamma

KW - Mice

KW - Mice, Inbred C3H

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Neovascularization, Pathologic

KW - Pancreatic Neoplasms

KW - Receptors, Tumor Necrosis Factor, Type I

KW - Signal Transduction

KW - Th1 Cells

KW - Time Factors

KW - Whole-Body Irradiation

U2 - 10.1016/j.ccr.2008.04.001

DO - 10.1016/j.ccr.2008.04.001

M3 - Article

C2 - 18538734

SN - 1535-6108

VL - 13

SP - 507

EP - 518

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -

TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis

Abstract

Keywords / Materials (for Non-textual outputs)

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