The Host Defense Peptide Cathelicidin Is Required for NK Cell-Mediated Suppression of Tumor Growth
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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.
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Although expressed in only very low levels in epidermal keratinocytes under resting conditions, cathelicidin is found in high levels in neutrophils, monocytes, natural killer cells, and T cells.
“Although expressed in only very low levels in epidermal keratinocytes under resting conditions, it is found in high levels in neutrophils, monocytes, natural killer (NK) cells, and T cells.40,41”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [41]
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The Innate Immune System in Acute and Chronic Wounds
MacLeod, A. S., & Mansbridge, J. N. (2016) · Advances in Wound Care · doi:10.1089/wound.2014.0608 · Cited by 289 · see citing works
“Although expressed in only very low levels in epidermal keratinocytes under resting conditions, it is found in high levels in neutrophils, monocytes, natural killer (NK) cells, and T cells.(40,41) Wound”
BackgroundDendritic epidermal T cells regulate skin antimicrobial barrier function
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- Authors
- Büchau, A. S., Morizane, S., Trowbridge, J., Schauber, J., Kotol, P., Bui, J. D., & Gallo, R. L.
- Affiliations
- VA San Diego Healthcare System (US)
- University of California San Diego (US)
- Corresponding author
- Morizane, Shin
- Trowbridge, Janet
- Kotol, Paul
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-12-14
- Volume
- 184
- Issue
- 1
- Pages
- 369-378
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC2908520
- OpenAlex
- W2171027071
- Cited by
- 73
- References
- 71
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 5 · 2018: 5 · 2017: 4 · 2016: 8 · 2015: 10 · 2014: 4 · 2013: 7 · 2012: 5
- FWCI
- 5.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (CA128893)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- cathelicidin, natural killer cells, antitumor immunity, tumor surveillance, tumor-infiltrating lymphocytes, NK cell cytotoxicity, perforin, interleukin-2, transplantable tumors, innate immunity
- MeSH terms
- Animals, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Immunologic Surveillance, Killer Cells, Natural, Melanoma, Experimental, Blotting, Western, Mice, Knockout, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Reverse Transcriptase Polymerase Chain Reaction, Xenograft Model Antitumor Assays, Antimicrobial Cationic Peptides, Mice, Cathelicidins
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