Document Detail


Immune modulation effects of concomitant temozolomide and radiation therapy on peripheral blood mononuclear cells in patients with glioblastoma multiforme.
MedLine Citation:
PMID:  21339188     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Concomitant radiation therapy (RT) and temozolomide (TMZ) therapy after surgery is the standard treatment for glioblastoma multiforme (GBM). Radiation and chemotherapy can affect the immune system with implications on subsequent immune therapy. Therefore, we examined the phenotype and function of peripheral blood mononuclear cells in 25 patients with GBM prior to and 4 weeks after treatment with RT-TMZ using multicolor flow cytometry, as well as in vitro CD4(+) regulatory T cell (T(reg)) suppressor and dendritic cell maturation assays. RT-TMZ induced significant lymphopenia, with a decrease in total CD4(+) T cells, but did not significantly change monocyte counts. The proportion of functional T(reg) cells increased after treatment, whereas their absolute numbers remained stable. There was also a measurable decrease in the proportion of CD8(+)CD56(+) and absolute number of CD3(-)CD56(+) effector cells. Posttherapy monocytes retained the ability to mature into dendritic cells. Treatment with RT-TMZ is associated with changes in regulatory and effector peripheral blood mononuclear cells that tilt the balance towards an immune suppressive state. This shift can affect the outcome of immune therapy following RT-TMZ treatment and should be considered in the design of future combination therapy regimens.
Authors:
Camilo E Fadul; Jan L Fisher; Jiang Gui; Thomas H Hampton; Anik L Côté; Marc S Ernstoff
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-20
Journal Detail:
Title:  Neuro-oncology     Volume:  13     ISSN:  1523-5866     ISO Abbreviation:  Neuro-oncology     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-24     Completed Date:  2011-07-26     Revised Date:  2013-08-08    
Medline Journal Info:
Nlm Unique ID:  100887420     Medline TA:  Neuro Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  393-400     Citation Subset:  IM    
Affiliation:
Department of Medicine, Section of Hematology/Oncology, Neuro-oncology Program, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA. camilo.e.fadul@hitchcock.org
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antineoplastic Agents, Alkylating / therapeutic use*
Blood Cells / drug effects,  immunology*,  radiation effects
Brain Neoplasms / drug therapy,  immunology,  radiotherapy
Combined Modality Therapy
Dacarbazine / analogs & derivatives*,  therapeutic use
Dendritic Cells / drug effects,  immunology,  radiation effects
Female
Flow Cytometry
Glioblastoma / drug therapy*,  immunology*,  radiotherapy*
Humans
Lymphocyte Subsets
Male
Middle Aged
Prognosis
Radiotherapy Dosage
T-Lymphocytes, Regulatory / drug effects,  immunology*,  radiation effects
Young Adult
Grant Support
ID/Acronym/Agency:
P20 RR016437/RR/NCRR NIH HHS; P20RR016437/RR/NCRR NIH HHS; P30 CA023108/CA/NCI NIH HHS; P42 ES007373/ES/NIEHS NIH HHS; P42ES007373/ES/NIEHS NIH HHS; R01 CA095648/CA/NCI NIH HHS; R01 CA095648/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Alkylating; 4342-03-4/Dacarbazine; 85622-93-1/temozolomide
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