Poor survival in glioblastoma patients is associated with early signs of immunosenescence in the CD4 T-cell compartment after surgery

• Published in: Oncoimmunology 2015-01, Vol.4 (9), p.e1036211-e1036211
• Main Authors: Fornara, Olesja, Odeberg, Jenny, Wolmer Solberg, Nina, Tammik, Charlotte, Skarman, Petra, Peredo, Inti, Stragliotto, Giuseppe, Rahbar, Afsar, Söderberg-Nauclér, Cecilia
• Format: Article
• Language: English
• Subjects: cytomegalovirus; glioblastoma; immunosenescence; Medicin och hälsovetenskap; Original Research; survival; T cells
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.1080/2162402X.2015.1036211

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.