Poor survival in glioblastoma patients is associated with early signs of immunosenescence in the CD4 T-cell compartment after surgery
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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 γδ 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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The low survival rate of patients with glioblastoma is associated with immunosenescence of postoperative CD4+ T cells.
“The low survival rate of patients with glioblastoma is associated with immunosenescence of postoperative CD4+ T cells [128].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [128]
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Lu, Y., Zhang, Q., Wang, J., & Zhang, L. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1118346 · Cited by 6 · see citing works
Cellular Components of the Tumor Environment in Gliomas—What Do We Know Today?
Nafe, R., & Hattingen, E. (2023) · Biomedicines · doi:10.3390/biomedicines12010014 · Cited by 4 · see citing works
Immunosenescence and Cancer Immunotherapy at Old Age: Basics
Fülöp, T., Witkowski, J. M., Hirokawa, K., Larbi, A., & Pawelec, G. (2018) · Springer eBooks · doi:10.1007/978-3-319-44870-1_77-1 · Cited by 4 · see citing works
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Vallejo-Bermúdez, I. M., Miranda-Echagüe, M. R., Fernández-Álvarez, S., Reina-Alfonso, I., Blanca-Pariente, L., Batista-Duharte, A., & Pera, A. (2026) · Cells · doi:10.3390/cells15050403 · Cited by 2 · see citing works
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Ellsworth, S. G., & Grossman, S. A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819755-4.00016-3 · Cited by 1 · see citing works
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Tur-Planells, V., Bykov, Y., Dawodu, G. O., Garcia‐Romero, N., Izpura-Luis, S., Pérez‐Rodríguez, L., Rius‐Rocabert, S., Palacín-Aliana, I., Arranz-Herrero, J., Márquez-Leiva, I., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-011741
Moritsubo, M., Furuta, T., Hashimoto, A., Yoshitake, H., Negoto, T., Nakamura, H., Morioka, M., & Miyoshi, H. (2026) · Neuropathology · doi:10.1111/neup.70071
- Authors
- Fornara, O., Odeberg, J., Wolmer Solberg, N., Tammik, C., Skarman, P., Peredo, I., Stragliotto, G., Rahbar, A., & Söderberg-Nauclér, C.
- Affiliations
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- Corresponding author
- Rahbar, Afsar
- Venue
- OncoImmunology
- Publisher
- Informa UK Limited
- Published
- 2015-06-05
- Volume
- 4
- Issue
- 9
- Pages
- e1036211
- ISSN
- 2162-4011 (ISSN-L)
- 2162-402X
- PMC
- PMC4570117
- OpenAlex
- W1569691540
- Cited by
- 45
- References
- 53
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 1
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- OncoImmunology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Familjen Erling-Perssons Stiftelse
- Swedish Cancer Foundation
- Biltema Foundation
- Svenska Sällskapet för Medicinsk Forskning
- Medical Research Council
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- glioblastoma, immunosenescence, CD4+ T cells, human cytomegalovirus infection, CD4+CD28- T cells, γδ T cells, CD4+CD25+ T cells, prognostic factors, survival, T cell subsets, immunosuppression
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