(1) Zhou Y (2) Heitmann JS (3) Clar KL (4) Kropp KN (5) Hinterleitner M (6) Engler T (7) Koch A (8) Hartkopf AD (9) Zender L (10) Salih HR (11) Maurer S (12) Hinterleitner C

Cancer immunology, immunotherapy

Owing to their key role in several diseases including cancer, activating and inhibitory immune checkpoint molecules are increasingly exploited as targets for immunotherapy. Recently, we demonstrated that platelets, which largely influence tumor progression and immune evasion, functionally express the ligand of the checkpoint molecule GITR. This immunoreceptor modulates effector functions of T cells and NK cells with its function varying dependent on cellular context and activation state. Here, we provide a comparative analysis of platelet-derived GITRL (pGITRL) in breast cancer patients and healthy volunteers. The levels of pGITRL were found to be higher on platelets derived from cancer patients and appeared to be specifically regulated during tumor progression as exemplified by several clinical parameters including tumor stage/grade, the occurrence of metastases and tumor proliferation (Ki67) index. In addition, we report that pGITRL is upregulated during platelet maturation and particularly induced upon exposure to tumor-derived soluble factors. Our data indicate that platelets modulate the GITR/GITRL immune checkpoint in the context of malignant disease and provide a rationale to further study the GITR/GITRL axis for exploitation for immunotherapeutic intervention in cancer patients.

Author Info: (1) Clinical Collaboration Unit Translational Immunology, Department of Internal Medicine, German Cancer Consortium (DKTK), University Hospital Tuebingen, Tuebingen, Germany. Clust

Author Info: (1) Clinical Collaboration Unit Translational Immunology, Department of Internal Medicine, German Cancer Consortium (DKTK), University Hospital Tuebingen, Tuebingen, Germany. Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Tuebingen, Germany. (2) Clinical Collaboration Unit Translational Immunology, Department of Internal Medicine, German Cancer Consortium (DKTK), University Hospital Tuebingen, Tuebingen, Germany. Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Tuebingen, Germany. (3) Clinical Collaboration Unit Translational Immunology, Department of Internal Medicine, German Cancer Consortium (DKTK), University Hospital Tuebingen, Tuebingen, Germany. Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Tuebingen, Germany. (4) Department of Hematology, Medical Oncology and Pneumology, University Medical Center of Mainz, Mainz, Germany. (5) Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Tuebingen, Germany. Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany. (6) Department of Obstetrics and Gynecology, University Hospital Tuebingen, Tuebingen, Germany. (7) Department of Obstetrics and Gynecology, University Hospital Tuebingen, Tuebingen, Germany. (8) Department of Obstetrics and Gynecology, University Hospital Tuebingen, Tuebingen, Germany. (9) Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Tuebingen, Germany. Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany. German Cancer Research Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site TŸbingen, Heidelberg, Germany. (10) Clinical Collaboration Unit Translational Immunology, Department of Internal Medicine, German Cancer Consortium (DKTK), University Hospital Tuebingen, Tuebingen, Germany. Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Tuebingen, Germany. (11) Clinical Collaboration Unit Translational Immunology, Department of Internal Medicine, German Cancer Consortium (DKTK), University Hospital Tuebingen, Tuebingen, Germany. stefanie.maurer@med.uni-tuebingen.de. Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Tuebingen, Germany. stefanie.maurer@med.uni-tuebingen.de. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. stefanie.maurer@med.uni-tuebingen.de. (12) Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Tuebingen, Germany. Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany.

Citation: Cancer Immunol Immunother 2021 Feb 4 Epub02/04/2021

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/33538861

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