Journal
ONCOIMMUNOLOGY
Volume 4, Issue 9, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2015.1036211
Keywords
cytomegalovirus; glioblastoma; immunosenescence; survival; T cells
Categories
Funding
- BILTEMA Foundation
- Stichting af Jochnicks Foundation
- Sten A Olssons Foundation for Research and Culture
- Familjen Erling-Perssons Stiftelse
- RATOS
- Hoffmann La Roche
- Torsten Foundation
- Ragnar Soderbergs Foundation
- Dan och Jane Olssons Foundation
- Swedish Cancer Foundation
- Swedish Medical Research Council
- Swedish Society for Medical Research (SLS)
- Goljes Memory Foundation
- Magnus Bergvalls Foundation
- Swedish Society for Medical Research (SSMF)
- IngaBritt och Arne Lundbergs Foundation
- Nexttobe
- Tore Nilsons Foundation
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Patients with glioblastoma multiforme (GBM) are immunosuppressed and have a broad range of immunological defects in both innate and adaptive immune responses. GBMs are frequently infected with human cytomegalovirus (HCMV), a virus capable of causing immunosuppression. In 42 HCMV-positive GBM patients in a clinical trial (VIGAS), we investigated T-cell phenotypes in the blood and assessed their relation to survival. Blood was collected before and 3, 12, and 24 weeks after surgery, and the frequency of T-cell subsets was compared with that in 26 age-matched healthy controls. GBM patients had lower levels of CD3 cells than the controls, but had significantly higher levels of CD4(+)CD28(-) T cells before and 3 and 12 weeks after surgery and increased levels of CD4(+)CD57(+) and CD4(+)CD57(+)CD28(+) T cells at all-time points. These T-cell subsets were associated with both immunosenescence and HCMV infection. GBM patients also had higher levels of gamma delta T cells at all-times after surgery and lower levels of CD4(+)CD25(+) cells before and 3 weeks after surgery than healthy controls. Overall survival was significantly shorter in patients with higher levels of CD4(+)CD28(-) T cells (p = 0.025), CD4(+)CD57(+) T (p = 0.025) cells, and CD4(+)CD28(-)CD57(+)CD28(-) T cells (p < 0.0004) at 3 weeks after surgery. Our findings indicate that signs of immunosenescence in the CD4(+) compartment are associated with poor prognosis in patients with HCMV-positive GBMs and may reflect the HCMV activity in their tumors.
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