PMID- 23828240
OWN - NLM
STAT- MEDLINE
DCOM- 20140218
LR  - 20220330
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 15
IP  - 8
DP  - 2013 Aug
TI  - Increase in tumor-associated macrophages after antiangiogenic therapy is 
      associated with poor survival among patients with recurrent glioblastoma.
PG  - 1079-87
LID - 10.1093/neuonc/not082 [doi]
AB  - Antiangiogenic therapy is associated with increased radiographic responses in 
      glioblastomas, but tumors invariably recur. Because tumor-associated macrophages 
      have been shown to mediate escape from antiangiogenic therapy in preclinical 
      models, we examined the role of macrophages in patients with recurrent 
      glioblastoma. We compared autopsy brain specimens from 20 patients with recurrent 
      glioblastoma who received antiangiogenic treatment and chemoradiation with 8 
      patients who received chemotherapy and/or radiotherapy without antiangiogenic 
      therapy or no treatment. Tumor-associated macrophages were morphologically and 
      phenotypically analyzed using flow cytometry and immunohistochemistry for CD68, 
      CD14, CD163, and CD11b expression. Flow cytometry showed an increase in 
      macrophages in the antiangiogenic-treated patients. Immunohistochemical analysis 
      demonstrated an increase in CD68+ macrophages in the tumor bulk (P < .01) and 
      infiltrative areas (P = .02) in antiangiogenic-treated patients. We also observed 
      an increase in CD11b+ cells in the tumor bulk (P < .01) and an increase in CD163+ 
      macrophages in infiltrative tumor (P = .02). Of note, an increased number of 
      CD11b+ cells in bulk and infiltrative tumors (P = .05 and P = .05, respectively) 
      correlated with poor overall survival among patients who first received 
      antiangiogenic therapy at recurrence. In summary, recurrent glioblastomas showed 
      an increased infiltration in myeloid populations in the tumor bulk and in the 
      infiltrative regions after antiangiogenic therapy. Higher numbers of CD11b+ cells 
      correlated with poor survival among these patients. These data suggest that 
      tumor-associated macrophages may participate in escape from antiangiogenic 
      therapy and may represent a potential biomarker of resistance and a potential 
      therapeutic target in recurrent glioblastoma.
FAU - Lu-Emerson, Christine
AU  - Lu-Emerson C
AD  - Department of Neurology, Radiation Oncology, Massachusetts General Hospital 
      Cancer Center and Harvard Medical School, Boston, MA, USA.
FAU - Snuderl, Matija
AU  - Snuderl M
FAU - Kirkpatrick, Nathaniel D
AU  - Kirkpatrick ND
FAU - Goveia, Jermaine
AU  - Goveia J
FAU - Davidson, Christian
AU  - Davidson C
FAU - Huang, Yuhui
AU  - Huang Y
FAU - Riedemann, Lars
AU  - Riedemann L
FAU - Taylor, Jennie
AU  - Taylor J
FAU - Ivy, Percy
AU  - Ivy P
FAU - Duda, Dan G
AU  - Duda DG
FAU - Ancukiewicz, Marek
AU  - Ancukiewicz M
FAU - Plotkin, Scott R
AU  - Plotkin SR
FAU - Chi, Andrew S
AU  - Chi AS
FAU - Gerstner, Elizabeth R
AU  - Gerstner ER
FAU - Eichler, April F
AU  - Eichler AF
FAU - Dietrich, Jorg
AU  - Dietrich J
FAU - Stemmer-Rachamimov, Anat O
AU  - Stemmer-Rachamimov AO
FAU - Batchelor, Tracy T
AU  - Batchelor TT
FAU - Jain, Rakesh K
AU  - Jain RK
LA  - eng
GR  - 8UL1TR000170-05/TR/NCATS NIH HHS/United States
GR  - R01CA159258/CA/NCI NIH HHS/United States
GR  - U01CA062490/CA/NCI NIH HHS/United States
GR  - P01 CA080124/CA/NCI NIH HHS/United States
GR  - R01CA129371/CA/NCI NIH HHS/United States
GR  - U01 CA154601/CA/NCI NIH HHS/United States
GR  - UL1 TR000170/TR/NCATS NIH HHS/United States
GR  - R01CA163815/CA/NCI NIH HHS/United States
GR  - P01CA080124/CA/NCI NIH HHS/United States
GR  - K12 CA090354/CA/NCI NIH HHS/United States
GR  - K24 CA125440/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 - 20130704
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antigens, CD)
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angiogenesis Inhibitors/*therapeutic use
MH  - Antigens, CD/metabolism
MH  - Autopsy
MH  - Biomarkers, Tumor/*metabolism
MH  - Brain Neoplasms/drug therapy/*mortality/pathology
MH  - Female
MH  - Flow Cytometry
MH  - Follow-Up Studies
MH  - Glioblastoma/drug therapy/*mortality/pathology
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Macrophages/drug effects/*pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Neoplasm Recurrence, Local/drug therapy/*mortality/pathology
MH  - Prognosis
MH  - Survival Rate
MH  - Tumor Microenvironment/*drug effects
MH  - Young Adult
PMC - PMC3714160
OTO - NOTNLM
OT  - antiangiogenic therapy
OT  - glioblastoma
OT  - myeloid cells
OT  - relapse
EDAT- 2013/07/06 06:00
MHDA- 2014/02/19 06:00
PMCR- 2014/08/01
CRDT- 2013/07/06 06:00
PHST- 2013/07/06 06:00 [entrez]
PHST- 2013/07/06 06:00 [pubmed]
PHST- 2014/02/19 06:00 [medline]
PHST- 2014/08/01 00:00 [pmc-release]
AID - not082 [pii]
AID - 10.1093/neuonc/not082 [doi]
PST - ppublish
SO  - Neuro Oncol. 2013 Aug;15(8):1079-87. doi: 10.1093/neuonc/not082. Epub 2013 Jul 4.