Project Details
Projekt
Innate Immunosurveillance of Metastatic Disease
Subject Area
Immunology
Pathology
Pathology
Term
from 2014 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 242727105
Cytotoxic immune cells have the capacity to identify and kill cancer cells, even at the stage of metastatic disease. Our group showed that natural killer cells (NK) and CD8 T cells, both cytotoxic effector cell populations, contribute to immunsurveillance of cancer in a T-bet dependent fashion. Furthermore, our data from a spontaneous murine cancer model suggests that primary tumour formation depends more on mutations necessary for immune escape than on further progression to metastasis. Immune stimulation however represents a powerful tool to interfere with the immune-cancer balance, as indicated by our own findings and current clinical trials.We postulate that the interaction between cancer cells and NK or CD8 T cells is dynamic and is shaped by adaptation on the one hand, but external modifications on the other. Within this proposal, we will identify immune escape strategies by metastases compared to primary tumours, to identify effective immune targets against metastasis formation. Furthermore, we will further analyze the role of exogenous interleukin 15 on cancer immunosurveillance, a substance that has dichotomous effects on immunsurveillance in our hands. Finally, we propose that the interaction between CD8 T cells and NK cells is especially relevant in immunotherapy, as both cell types thrive from similar cytokine resources and might have both competing and synergistic effects.
DFG Programme
Research Units
