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Cited by 347Immune cells in cancerAngiogenesis and VEGF in CancerCancer Cells and Metastasis

Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment

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Ahn, G-One, Tseng, Diane, Liao, Cho-Hwa, Dorie, Mary Jo, Czechowicz, Agnieszka, Brown, J. Martin·2010·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0911378107PMC PMC2889597
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Abstract

Despite recent advances in radiotherapy, loco-regional failures are still the leading cause of death in many cancer patients. We have previously reported that bone marrow-derived CD11b + myeloid cells are recruited to tumors grown in irradiated tissues, thereby restoring the vasculature and tumor growth. In this study, we examined whether neutralizing CD11b monoclonal antibodies could inhibit the recruitment of myeloid cells into irradiated tumors and inhibit their regrowth. We observed a significant enhancement of antitumor response to radiation in squamous cell carcinoma xenografts in mice when CD11b antibodies are administered systemically. Histological examination of tumors revealed that CD11b antibodies reduced infiltration of myeloid cells expressing S100A8 and matrix metalloproteinase-9. CD11b antibodies further inhibited bone marrow-derived cell adhesion and transmigration to C166 endothelial cell monolayers and chemotactic stimuli, respectively, to levels comparable to those from CD11b knockout or CD18 hypomorphic mice. Given the clinical availability of humanized CD18 antibodies, we tested two murine tumor models in CD18 hypomorphic or CD11b knockout mice and found that tumors were more sensitive to irradiation when grown in CD18 hypomorphic mice but not in CD11b knockout mice. When CD18 hypomorphism was partially rescued by reconstitution with the wild-type bone marrow, the resistance of the tumors to irradiation was restored. Our study thus supports the rationale of using clinically available Mac-1 (CD11b/CD18) antibodies as an adjuvant therapy to radiotherapy.

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Cited by

Sorted by citations

Authors
Ahn, G.-O., Tseng, D., Liao, C.-H., Dorie, M. J., Czechowicz, A., & Brown, J. M.
Affiliations
  • Division of Radiation and Cancer Biology, Department of Radiation Oncology, and
  • Stanford Medicine (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2010-04-19
Volume
107
Issue
18
Pages
8363-8368
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0911378107
PMC
PMC2889597
OpenAlex
W2089260704
Cited by
347
References
0
Citations by year
2026: 6 · 2025: 13 · 2024: 14 · 2023: 15 · 2022: 14 · 2021: 23 · 2020: 26 · 2019: 24 · 2018: 22 · 2017: 34 · 2016: 25 · 2015: 20 · 2014: 23 · 2013: 37 · 2012: 24
FWCI
11.94
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion, cc-by-nc-nd)
Funders
  • Paul and Daisy Soros Fellowships for New Americans
  • National Science Council
  • Pohang University of Science and Technology
  • National Institutes of Health
  • School of Medicine, Stanford University
  • University of California, San Francisco
  • National Cancer Institute (R01CA128873, CA128873)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
Mac-1, CD11b/CD18, myeloid cell recruitment, bone marrow-derived myeloid cells, S100A8, MMP-9, tumor recurrence
MeSH terms
Animals, Antibodies, Carcinoma, Squamous Cell, Cell Line, Cell Movement, Disease Models, Animal, Humans, Mice, Nude, Recurrence, Macrophage-1 Antigen, Mice, Knockout, CD18 Antigens, Myeloid Cells, Xenograft Model Antitumor Assays, CD11b Antigen, Mice

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