Microparticles from tumors exposed to radiation promote immune evasion in part by PD-L1
| Autor: | Ruslana Kotsofruk, Elisabeth G.E. de Vries, Tongwu Zhang, Yuval Shaked, Orit Kaidar-Person, Michael Timaner, Tal Kan, Shahar Daniel, Robert S. Kerbel, Ziv Raviv, A. Nevelsky, Dvir Shechter, Ksenia Magidey |
|---|---|
| Přispěvatelé: | Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Adoptive cell transfer medicine.medical_treatment Programmed Cell Death 1 Receptor MICROENVIRONMENT B7-H1 Antigen Mice 0302 clinical medicine Cell-Derived Microparticles Cytotoxic T cell ASSAY MICROVESICLES biology 3. Good health Cancer therapeutic resistance 030220 oncology & carcinogenesis Heterografts Female Signal Transduction RADIOTHERAPY EXPRESSION CANCER-THERAPY Breast Neoplasms Article MECHANISMS Immunomodulation 03 medical and health sciences Immune system In vivo Cell Line Tumor PD-L1 Genetics medicine Animals Humans Molecular Biology Immune Evasion Immunosurveillance Cancer medicine.disease Radiation therapy CTL 030104 developmental biology CELLS biology.protein Cancer research MEDIATORS T-Lymphocytes Cytotoxic RESPONSES |
| Zdroj: | Oncogene ONCOGENE, 39(1), 187-203. Nature Publishing Group |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | Radiotherapy induces immune-related responses in cancer patients by various mechanisms. Here, we investigate the immunomodulatory role of tumor-derived microparticles (TMPs)—extracellular vesicles shed from tumor cells—following radiotherapy. We demonstrate that breast carcinoma cells exposed to radiation shed TMPs containing elevated levels of immune-modulating proteins, one of which is programmed death-ligand 1 (PD-L1). These TMPs inhibit cytotoxic T lymphocyte (CTL) activity both in vitro and in vivo, and thus promote tumor growth. Evidently, adoptive transfer of CTLs pre-cultured with TMPs from irradiated breast carcinoma cells increases tumor growth rates in mice recipients in comparison with control mice receiving CTLs pre-cultured with TMPs from untreated tumor cells. In addition, blocking the PD-1-PD-L1 axis, either genetically or pharmacologically, partially alleviates TMP-mediated inhibition of CTL activity, suggesting that the immunomodulatory effects of TMPs in response to radiotherapy is mediated, in part, by PD-L1. Overall, our findings provide mechanistic insights into the tumor immune surveillance state in response to radiotherapy and suggest a therapeutic synergy between radiotherapy and immune checkpoint inhibitors. |
| Databáze: | OpenAIRE |
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