Profiling of Tumor-Infiltrating Immune Cells and Their Impact on Survival in Glioblastoma Patients Undergoing Immunotherapy with Dendritic Cells.
Nataly PeresGuilherme A LepskiCarla S FogolinGabriela Coeli Menezes EvangelistaElizabeth A FlatowJaqueline Vaz de OliveiraMariana Pereira PinhoPatricia C Bergami-SantosJosé Alexandre Marzagão BarbutoPublished in: International journal of molecular sciences (2024)
Glioblastomas (GBM) are the most common primary malignant brain tumors, comprising 2% of all cancers in adults. Their location and cellular and molecular heterogeneity, along with their highly infiltrative nature, make their treatment challenging. Recently, our research group reported promising results from a prospective phase II clinical trial involving allogeneic vaccination with dendritic cells (DCs). To date, six out of the thirty-seven reported cases remain alive without tumor recurrence. In this study, we focused on the characterization of infiltrating immune cells observed at the time of surgical resection. An analytical model employing a neural network-based predictive algorithm was used to ascertain the potential prognostic implications of immunological variables on patients' overall survival. Counterintuitively, immune phenotyping of tumor-associated macrophages (TAMs) has revealed the extracellular marker PD-L1 to be a positive predictor of overall survival. In contrast, the elevated expression of CD86 within this cellular subset emerged as a negative prognostic indicator. Fundamentally, the neural network algorithm outlined here allows a prediction of the responsiveness of patients undergoing dendritic cell vaccination in terms of overall survival based on clinical parameters and the profile of infiltrated TAMs observed at the time of tumor excision.
Keyphrases
- dendritic cells
- neural network
- clinical trial
- patients undergoing
- phase ii
- free survival
- immune response
- regulatory t cells
- end stage renal disease
- single cell
- machine learning
- open label
- ejection fraction
- newly diagnosed
- chronic kidney disease
- stem cell transplantation
- bone marrow
- deep learning
- randomized controlled trial
- magnetic resonance
- study protocol
- magnetic resonance imaging
- double blind
- risk assessment
- phase iii
- patient reported
- high dose