Densely Granulated Murine NK Cells Eradicate Large Solid Tumors
| Autor: | Karin Schreiber, Andrea Schietinger, David C. Binder, Bana Jabri, Donald A. Rowley, Thomas Krausz, Boris Engels, Hans Schreiber, Ainhoa Arina, Rebecca B. Liu, Eric A. Butz, Elizabeth Hyjek |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Stromal cell Enzyme-Linked Immunosorbent Assay macromolecular substances Biology Lymphocyte Activation Article Mice Interleukin 21 NK-92 Tumor Microenvironment medicine Animals Inclusion Bodies Interleukin-15 Mice Knockout Tumor microenvironment Lymphokine-activated killer cell Janus kinase 3 Neoplasms Experimental Flow Cytometry Immunohistochemistry Killer Cells Natural Oncology Cancer cell Cancer research Interleukin 12 |
| Zdroj: | Cancer Research. 72:1964-1974 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-11-3208 |
| Popis: | Natural killer (NK) cells inhibit early stages of tumor formation, recurrence, and metastasis. Here, we show that NK cells can also eradicate large solid tumors. Eradication depended on the massive infiltration of proliferating NK cells due to interleukin 15 (IL-15) released and presented by the cancer cells in the tumor microenvironment. Infiltrating NK cells had the striking morphologic feature of being densely loaded with periodic acid-Schiff–positive, diastase-resistant granules, resembling uterine NK cells. Perforin-mediated killing by these densely granulated NK cells was essential for tumor eradication. Expression of the IL-15 receptor α on cancer cells was needed to efficiently induce granulated NK cells, and expression on host stromal cells was essential to prevent tumor relapse after near complete destruction. These results indicate that IL-15 released at the cancer site induces highly activated NK cells that lead to eradication of large solid tumors. Cancer Res; 72(8); 1964–74. ©2012 AACR. |
| Databáze: | OpenAIRE |
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