PD-L1 tumor expression is associated with poor prognosis and systemic immunosuppression in glioblastoma

Autores da FMUP

• Dina Raquel Aguileira Leitão

  Autor

• 

  Fernando Carlos De Landér Schmitt

  Autor

• Joana Cancela De Amorim Falcão Paredes

  Autor

Participantes de fora da FMUP

• Noronha, C
• Ribeiro, AS
• Taipa, R
• Reis, J
• Faria, C

Unidades de investigação

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Patologia

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Purpose Glioblastoma is the most common primary malignant brain tumor in the adult, whose grim prognosis largely relates to the absence of effective treatment targets. Given its success in other cancers, immunotherapy has been trialed in glioblastoma and failed to demonstrate the expected benefit. Importantly, these disappointing results highlight the importance of understanding the unique and transforming biology of glioblastoma and its microenvironment. Our goal was to evaluate and characterize the expression of PD-L1 through immunohistochemistry in a large glioblastoma cohort. We further studied PD-L1 expression-associated prognosis and its correlation to systemic and neuropathological parameters. Methods A series of 352 glioblastoma specimens (313 initial resection, 39 matched recurrences) was collected, with a detailed characterization of tumor neuropathological characteristics, including the presence, density and location of tumor infiltrating lymphocytes (TIL). Two hematological markers, absolute lymphocyte count and neutrophil-lymphocyte ratio (NLR), were used to analyze and correlate with systemic inflammation and immunosuppression. Immunohistochemistry was performed to evaluate PD-L1 expression. Results Membranous PD-L1 expression was identified in 31% (98/313) of newly diagnosed and 46% (18/39) of matched recurrent tumors. TIL were found in 26% (82/313) of primary tumors and both density and location were found to be significantly associated with PD-L1 expression (p < 0.001). Interestingly, PD-L1 expressing tumors had more frequently areas with sarcomatous differentiation (p < 0.001) and were significantly associated with lower lymphocyte count (p = 0.018) and higher NLR ratio (p = 0.004) upon diagnosis. Importantly, PD-L1 expression was an independent poor prognostic marker in our cohort. Conclusion Taken together, our data points to a putative role for PD-L1 expression in glioblastoma biology, which correlates to poor patient overall survival, as well as with a general systemic inflammatory status and immunosuppression.

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

• Glioblastoma; PD-L1; Tumor infiltrating lymphocytes (TIL); Neutrophil-lymphocyte ratio (NLR); Lymphocytopenia