Control of tumor-specific T cell responses through regulatory T cells (B)

• Subject Area: Hematology, Oncology
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 178696424

Spontaneous T cell (TC) responses against cancer play a pivotal role during tumor induction, progression and relapse. Studying the prognostic significance of spontaneous TA-specific TC in colorectal cancer (CRC) patients we identified in situ active, TNF-alphapos Teff as the TIL population that determines protection from tumor relapse and long term survival. We showed that tumor-associated macrophages (TAM) educate endothelial cells in the tumor vasculature to aquire an "anergic" phenotype that prevented Teff immigration and in situ function by supporting the entry of Treg. Within the upcoming funding period we will study the cellular basis and micro-environmental context that orchestrate the local composition and functional activity of the tumors immune infiltrates with a focus on TNF-alphapos TIL clones and their influence by TAM, Treg and the tumor vasculature.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 938: Environment Specific Control of Immunological Reactivity
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Co-Applicant Institution: Deutsches Krebsforschungszentrum (DKFZ); Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg – DKFZ
• Project Heads: Professor Dr. Philipp Beckhove; Professor Dr. Dirk Jäger