title: Poor survival in glioblastoma patients is associated with early signs of immunosenescence in the CD4 T-cell compartment after surgery.
abstract: 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.
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Olesja
authors.initials: O
authors.lastname: Fornara
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Odeberg
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Wolmer Solberg
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Tammik
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Petra
authors.initials: P
authors.lastname: Skarman
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden ; Department of Neurosurgery; Karolinska University Hospital ; Stockholm, Sweden.
authors.forename: Inti
authors.initials: I
authors.lastname: Peredo
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden ; Department of Neuropathology; Karolinska University Hospital ; Stockholm, Sweden.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Stragliotto
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Afsar
authors.initials: A
authors.lastname: Rahbar
authors.affiliation: Department of Medicine; Solna; Center for Molecular Medicine; Karolinska Institute ; Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Söderberg-Nauclér
keywords: T cells; cytomegalovirus; glioblastoma; immunosenescence; survival