PMID- 20404138
OWN - NLM
STAT- MEDLINE
DCOM- 20100608
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 107
IP  - 18
DP  - 2010 May 4
TI  - Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing 
      myeloid cell recruitment.
PG  - 8363-8
LID - 10.1073/pnas.0911378107 [doi]
AB  - 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.
FAU - Ahn, G-One
AU  - Ahn GO
AD  - Division of Radiation and Cancer Biology, Department of Radiation Oncology, 
      Stanford University School of Medicine, Stanford, CA 94305, USA.
FAU - Tseng, Diane
AU  - Tseng D
FAU - Liao, Cho-Hwa
AU  - Liao CH
FAU - Dorie, Mary Jo
AU  - Dorie MJ
FAU - Czechowicz, Agnieszka
AU  - Czechowicz A
FAU - Brown, J Martin
AU  - Brown JM
LA  - eng
GR  - R01 CA128873/CA/NCI NIH HHS/United States
GR  - CA128873/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100419
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antibodies)
RN  - 0 (CD11b Antigen)
RN  - 0 (CD18 Antigens)
RN  - 0 (Macrophage-1 Antigen)
SB  - IM
MH  - Animals
MH  - Antibodies/immunology
MH  - CD11b Antigen/*immunology
MH  - CD18 Antigens/*immunology
MH  - Carcinoma, Squamous Cell/blood supply/*immunology/pathology/radiotherapy
MH  - Cell Line
MH  - *Cell Movement
MH  - Disease Models, Animal
MH  - Humans
MH  - Macrophage-1 Antigen/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Nude
MH  - Myeloid Cells/cytology/*immunology/radiation effects
MH  - Recurrence
MH  - Xenograft Model Antitumor Assays
PMC - PMC2889597
COIS- The authors declare no conflict of interest.
EDAT- 2010/04/21 06:00
MHDA- 2010/06/09 06:00
PMCR- 2010/11/04
CRDT- 2010/04/21 06:00
PHST- 2010/04/21 06:00 [entrez]
PHST- 2010/04/21 06:00 [pubmed]
PHST- 2010/06/09 06:00 [medline]
PHST- 2010/11/04 00:00 [pmc-release]
AID - 0911378107 [pii]
AID - 200911378 [pii]
AID - 10.1073/pnas.0911378107 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2010 May 4;107(18):8363-8. doi: 
      10.1073/pnas.0911378107. Epub 2010 Apr 19.