Project Details
Projekt
KFO 124: The Tumor Microenvironment
Subject Area
Medicine
Term
from 2004 to 2010
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5397363
The limited efficacy of chemotherapeutic agents and radiation in the treatment of the majority of solid tumors calls for new therapeutic strategies. The identification of immunogenic tumor-specific antigens suggested immunotherapeutic approaches as a promising treatment options. Unfortunately, immunotherapy has so far failed to live up to this promise.
Therapeutic vaccination in oncology aims at the induction of specific immune responses capable of eradicating the neoplastic cells. Hence, it is not surprising that most of current approaches use tumor-associated antigens expressed by the neoplastic cells themselves as a target. Due to genetic instability, reduced expression of molecules necessary to present the corresponding antigens to the immune system as well as several direct and indirect immune escape mechanisms, the tumor cell itself seems to be a difficult target for immunologic eradication. In this respect, it should be noted that tumors are not simply an accumulation of neoplastic cells, but rather complicated organs with blood vessels, stromal cells, infiltrating immune competent cells and a differentiated extracellular matrix. Hence, the tumor microenvironment may serve as an additional source for targets of therapeutic immune responses. Moreover, it has become obvious that the tumor microenvironment is an important modulator of ongoing tumor-specific immune responses. The modulation is both direct, i.e. inflicting the activity of tumor infiltrating lymphocytes, as indirect, e.g. changing the function of antigen presenting cells. Interestingly, very similar mechanisms seem to be involved in several physiologic situations such as maintaining peripheral tolerance to self antigens or avoiding immune reactions during pregnancy.
The goal of projected work is the analysis of ongoing anti-tumor immune responses "in situ" in the context of the tumor microenvironment. By means of newly developed cellular and molecular techniques it is intended to gain a comprehensive understanding of the immunological relevant processes governing the outcome of immune responses to solid tumors. This knowledge should allow improving the efficacy of immune therapy for malignant disease. In addition, tumor-stroma associated antigens will be evaluated for their therapeutic potential.
Therapeutic vaccination in oncology aims at the induction of specific immune responses capable of eradicating the neoplastic cells. Hence, it is not surprising that most of current approaches use tumor-associated antigens expressed by the neoplastic cells themselves as a target. Due to genetic instability, reduced expression of molecules necessary to present the corresponding antigens to the immune system as well as several direct and indirect immune escape mechanisms, the tumor cell itself seems to be a difficult target for immunologic eradication. In this respect, it should be noted that tumors are not simply an accumulation of neoplastic cells, but rather complicated organs with blood vessels, stromal cells, infiltrating immune competent cells and a differentiated extracellular matrix. Hence, the tumor microenvironment may serve as an additional source for targets of therapeutic immune responses. Moreover, it has become obvious that the tumor microenvironment is an important modulator of ongoing tumor-specific immune responses. The modulation is both direct, i.e. inflicting the activity of tumor infiltrating lymphocytes, as indirect, e.g. changing the function of antigen presenting cells. Interestingly, very similar mechanisms seem to be involved in several physiologic situations such as maintaining peripheral tolerance to self antigens or avoiding immune reactions during pregnancy.
The goal of projected work is the analysis of ongoing anti-tumor immune responses "in situ" in the context of the tumor microenvironment. By means of newly developed cellular and molecular techniques it is intended to gain a comprehensive understanding of the immunological relevant processes governing the outcome of immune responses to solid tumors. This knowledge should allow improving the efficacy of immune therapy for malignant disease. In addition, tumor-stroma associated antigens will be evaluated for their therapeutic potential.
DFG Programme
Clinical Research Units
Projects
- Charakterisierung der tumorinduzierten Immunsuppression beim Glukokortikoid-sezernierenden Nebennierenrindenkarzinom (Applicant Fassnacht, Martin )
- Charakterisierung immunmodulierender Faktoren im Mikromilieu des Tumors (Applicant Eggert, Andreas )
- Das Tumormikromilieu: Zielstruktur und Modulator von Immunantworten (Applicant Bröcker, Eva-Bettina )
- Die Plazentation beim Menschen als Modell für die Immunregulation invasiver Tumoren (Applicant Kämmerer, Ulrike )
- Einfluss der Natur von Antigenen auf die Entwicklung von Effektor- und Gedächtnisimmunantworten (Applicant Schrama, David )
- gamma delta T-Zellen im Tumormikromilieu - Modulation der Tumorantigenspezifischen alpha beta T-Zell Immunantwort durch gamma delta T-Zellen (Applicant Kunzmann, Volker )
- Identifikation und Evalution von HLA-restringierten T-Zell-Epitopen, welche sich von onkogenen Proteinen der Tumorzellen, des Tumorstroma bzw. des Tumorendothels ableiten (Applicant Becker, Jürgen Christian )
- "Trogozytose" immuntolerogener Moleküle als Mechanismus zur Modulation von Tumor-Immunzellinteraktionen (Applicant Wiendl, Heinz )
- Visualisierung der Effektorfunktion zytotoxischer T-Zellen in komplexen soliden Tumoren: Einfluss des Mikromilieus auf die T-Zell-Tumor-Interaktion und serielles Killing in vitro und in vivo (Applicant Friedl, Peter )
Spokesperson
Professorin Dr. Eva-Bettina Bröcker
