Frontiers in Oncology (Jul 2022)
Controversial Role of the Immune Checkpoint OX40L Expression on Platelets in Breast Cancer Progression
- Susanne M. Rittig,
- Susanne M. Rittig,
- Martina S. Lutz,
- Martina S. Lutz,
- Kim L. Clar,
- Kim L. Clar,
- Yanjun Zhou,
- Yanjun Zhou,
- Korbinian N. Kropp,
- André Koch,
- Andreas D. Hartkopf,
- Andreas D. Hartkopf,
- Martina Hinterleitner,
- Martina Hinterleitner,
- Lars Zender,
- Lars Zender,
- Lars Zender,
- Helmut R. Salih,
- Helmut R. Salih,
- Stefanie Maurer,
- Stefanie Maurer,
- Stefanie Maurer,
- Clemens Hinterleitner,
- Clemens Hinterleitner,
- Clemens Hinterleitner
Affiliations
- Susanne M. Rittig
- Department of Hematology, Oncology and Cancer Immunology, Charité – Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Berlin, Germany
- Susanne M. Rittig
- Berlin Institute of Health at Charité – Universitaetsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité (Junior) (Digital) Clinician Scientist Program, Berlin, Germany
- Martina S. Lutz
- Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, Germany
- Martina S. Lutz
- Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies” , University of Tuebingen, Tuebingen, Germany
- Kim L. Clar
- Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, Germany
- Kim L. Clar
- Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies” , University of Tuebingen, Tuebingen, Germany
- Yanjun Zhou
- Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, Germany
- Yanjun Zhou
- Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies” , University of Tuebingen, Tuebingen, Germany
- Korbinian N. Kropp
- Department of Hematology, Medical Oncology and Pneumology, University Medical Center of Mainz, Mainz, Germany
- André Koch
- Department of Obstetrics and Gynecology, University Hospital Tuebingen, Tuebingen, Germany
- Andreas D. Hartkopf
- Department of Obstetrics and Gynecology, University Hospital Tuebingen, Tuebingen, Germany
- Andreas D. Hartkopf
- Department of Gynecology and Obstetrics, University Hospital of Ulm, Ulm, Germany
- Martina Hinterleitner
- Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies” , University of Tuebingen, Tuebingen, Germany
- Martina Hinterleitner
- Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany
- Lars Zender
- Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies” , University of Tuebingen, Tuebingen, Germany
- Lars Zender
- Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany
- Lars Zender
- German Cancer Research Consortium (DKTK), Partner Site Tuebingen, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Helmut R. Salih
- Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, Germany
- Helmut R. Salih
- Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies” , University of Tuebingen, Tuebingen, Germany
- Stefanie Maurer
- Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, Germany
- Stefanie Maurer
- Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies” , University of Tuebingen, Tuebingen, Germany
- Stefanie Maurer
- 0Precision Immunology Institute, Department of Oncological Sciences, and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Clemens Hinterleitner
- Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies” , University of Tuebingen, Tuebingen, Germany
- Clemens Hinterleitner
- Department of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen, Germany
- Clemens Hinterleitner
- 1Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, United States
- DOI
- https://doi.org/10.3389/fonc.2022.917834
- Journal volume & issue
-
Vol. 12
Abstract
In conventional T cells, OX40 has been identified as a major costimulating receptor augmenting survival and clonal expansion of effector and memory T cell populations. In regulatory T cells, (Treg) OX40 signaling suppresses cellular activity and differentiation. However, clinical trials investigating OX40 agonists to enhance anti-tumor immunity, showed only limited success so far. Here we show that platelets from breast cancer patients express relevant levels of OX40L and platelet OX40L (pOX40L) inversely correlates with platelet-expressed immune checkpoint molecules GITRL (pGITRL) and TACI (pTACI). While high expression of pOX40L correlates with T and NK cell activation, elevated pOX40L levels identify patients with higher tumor grades, the occurrence of metastases, and shorter recurrence-free survival (RFS). Of note, OX40 mRNA levels in breast cancer correlate with enhanced expression of anti-apoptotic, immune-suppressive, and tumor-promoting mRNA gene signatures. Our data suggest that OX40L on platelets might play counteracting roles in cancer and anti-tumor immunity. Since pOX40L reflects disease relapse better than the routinely used predictive markers CA15-3, CEA, and LDH, it could serve as a novel biomarker for refractory disease in breast cancer.
Keywords
