The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved Jigsaw

Genes (Basel). 2023 Feb 15;14(2):501. doi: 10.3390/genes14020501.

Abstract

Despite the adoption of novel therapeutical approaches, the outcomes for glioblastoma (GBM) patients remain poor. In the present study, we investigated the prognostic impact of several clinico-pathological and molecular features as well as the role of the cellular immune response in a series of 59 GBM. CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) were digitally assessed on tissue microarray cores and their prognostic role was investigated. Moreover, the impact of other clinico-pathological features was evaluated. The number of CD4+ and CD8+ is higher in GBM tissue compared to normal brain tissue (p < 0.0001 and p = 0.0005 respectively). A positive correlation between CD4+ and CD8+ in GBM is present (rs = 0.417-p = 0.001). CD4+ TILs are inversely related to overall survival (OS) (HR = 1.79, 95% CI 1.1-3.1, p = 0.035). The presence of low CD4+ TILs combined with low CD8+ TILs is an independent predictor of longer OS (HR 0.38, 95% CI 0.18-0.79, p = 0.014). Female sex is independently related to longer OS (HR 0.42, 95% CI 0.22-0.77, p = 0.006). Adjuvant treatment, methylguanine methyltransferase (MGMT) promoter methylation, and age remain important prognostic factors but are influenced by other features. Adaptive cell-mediated immunity can affect the outcomes of GBM patients. Further studies are needed to elucidate the commitment of the CD4+ cells and the effects of different TILs subpopulations in GBM.

Keywords: CD4; CD8; TILs; gender; glioblastoma; microenvironment; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / pathology
  • Female
  • Glioblastoma* / pathology
  • Humans
  • Lymphocytes, Tumor-Infiltrating
  • Prognosis

Grants and funding

The project was supported by the project infrastructure POIG.02.03.00-14-111/13 funded by the Operational Programme Innovative Economy 2007–2013, Priority II. R&D Infrastructure, Measure 2.3. Investments connected with the development of the IT Infrastructure of Science. G.N.F. is supported as Junior Assistant Professor/Temporary Researcher (RTDA) by the Italian Ministry of University and Research—PON “Research and Innovation” 2014–2020 (PON R&I) Actions IV. 4 “Doctorates and research contracts on innovation topics”.