The host defense peptide cathelicidin is required for NK cell-mediated suppression of tumor growth

Amanda S. Büchau, Shin Morizane, Janet Trowbridge, Jürgen Schauber, Paul Kotol, Jack D. Bui, Richard L. Gallo

Research output: Contribution to journalArticle

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Abstract

Tumor surveillance requires the interaction of multiple molecules and cells that participate in innate and the adaptive immunity. Cathelicidin was initially identified as an antimicrobial peptide, although it is now clear that it fulfills a variety of immune functions beyond microbial killing. Recent data have suggested contrasting roles for cathelicidin in tumor development. Because its role in tumor surveillance is not well understood, we investigated the requirement of cathelicidin in controlling transplantable tumors in mice. Cathelicidin was observed to be abundant in tumor-infiltrating NK1.1+ cells in mice. The importance of this finding was demonstrated by the fact that cathelicidin knockout mice (Camp-/-) permitted faster tumor growth than wild type controls in two different xenograft tumor mouse models (B16.F10 and RMA-S). Functional in vitro analyses found that NK cells derived from Camp-/- versus wild type mice showed impaired cytotoxic activity toward tumor targets. These findings could not be solely attributed to an observed perforin deficiency in freshly isolated Camp-/- NK cells, because this deficiency could be partially restored by IL-2 treatment, whereas cytotoxic activity was still defective in IL-2-activated Camp-/- NK cells. Thus, we demonstrate a previously unrecognized role of cathelicidin in NK cell antitumor function.

Original languageEnglish
Pages (from-to)369-378
Number of pages10
JournalJournal of Immunology
Volume184
Issue number1
DOIs
Publication statusPublished - Jan 1 2010
Externally publishedYes

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Natural Killer Cells
Peptides
Growth
Neoplasms
Interleukin-2
Perforin
CAP18 lipopolysaccharide-binding protein
Adaptive Immunity
Heterografts
Innate Immunity
Knockout Mice

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

The host defense peptide cathelicidin is required for NK cell-mediated suppression of tumor growth. / Büchau, Amanda S.; Morizane, Shin; Trowbridge, Janet; Schauber, Jürgen; Kotol, Paul; Bui, Jack D.; Gallo, Richard L.

In: Journal of Immunology, Vol. 184, No. 1, 01.01.2010, p. 369-378.

Research output: Contribution to journalArticle

Büchau, Amanda S. ; Morizane, Shin ; Trowbridge, Janet ; Schauber, Jürgen ; Kotol, Paul ; Bui, Jack D. ; Gallo, Richard L. / The host defense peptide cathelicidin is required for NK cell-mediated suppression of tumor growth. In: Journal of Immunology. 2010 ; Vol. 184, No. 1. pp. 369-378.
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