Densely granulated murine NK cells eradicate large solid tumors.

Abstract

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.

• Authors: Rebecca B Liu, Boris Engels, Ainhoa Arina, Karin Schreiber, Elizabeth Hyjek, Andrea Schietinger, David C Binder, Eric Butz, Thomas Krausz, Donald A Rowley, Bana Jabri, Hans Schreiber
• Journal: Cancer research (Cancer Res) Vol. 72 Issue 8 Pg. 1964-74 (Apr 15 2012) ISSN: 1538-7445 [Electronic] United States
• PMID: 22374983 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-15

Topics

• Animals
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Immunohistochemistry
• Inclusion Bodies
• Interleukin-15 (immunology, metabolism)
• Killer Cells, Natural (immunology, metabolism)
• Lymphocyte Activation (immunology)
• Mice
• Mice, Knockout
• Neoplasms, Experimental (immunology, metabolism)
• Tumor Microenvironment (immunology)