Refine
Has Fulltext
- yes (10)
Is part of the Bibliography
- yes (10)
Year of publication
Document Type
- Journal article (9)
- Conference Proceeding (1)
Language
- English (10)
Keywords
- TRAIL (2)
- acute myeloid leukemia (2)
- apoptosis (2)
- 1994> (1)
- BCOR (1)
- BCORL1 (1)
- CD27 (1)
- CD40 (1)
- CD70 (1)
- CML (1)
- Cancer genetics (1)
- Genetics research (1)
- Kongreß (1)
- Millimeterwelle (1)
- San Diego <Calif. (1)
- T cells (1)
- alleles (1)
- allogeneic hematopoietic stem cell transplantation (1)
- cancer microenvironment (1)
- chronic myeloid leukemia (1)
- consortium (1)
- cytarabine dose (1)
- dendritic cells (1)
- drug treatment (1)
- elderly (1)
- genetic modifiers (1)
- genome-wide association (1)
- hormone-related protein (1)
- immunotherapy (1)
- investigators (1)
- loss-of-function (1)
- mammographic density (1)
- ovarian cancer (1)
- risk stratification (1)
- scFv (1)
- stem cell transplantation (1)
- survival (1)
- susceptibility loci (1)
- tumor subtypes (1)
- tumour immunology (1)
- tyrosine kinase inhibitors (1)
Institute
- Medizinische Klinik und Poliklinik II (4)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (2)
- Physikalisches Institut (2)
- Frauenklinik und Poliklinik (1)
- Institut für Humangenetik (1)
- Institut für Virologie und Immunbiologie (1)
- Kinderklinik und Poliklinik (1)
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie (1)
- Medizinische Klinik und Poliklinik I (1)
- Theodor-Boveri-Institut für Biowissenschaften (1)
EU-Project number / Contract (GA) number
- 223175 (1)
Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don’t respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.