In Glioblastoma (GBM), monocytes recruited to the tumor site are emerging as one of the main culprits of immune suppression and are associated with a worse prognosis compared to brain tumors with low peripheral immune cell infiltration. During tumor initiation, microglia create an inflammatory environment which promotes growth. As tumors progress to malignancy, disruption of the blood brain barrier contributes to the release of mediators produced by neoplastic cells and the tumor microenvironment into the bloodstream. These factors induce the mobilization and recruitment of peripheral monocytes to the tumor site, which stimulate angiogenesis, enhance tumor cell migration and suppress anti-tumor immunity. Here, we aim to elucidate the transcriptional signatures of blood monocytic subpopulations, which are recruited to the tumor site along GBM progression from the bone marrow and the spleen. We strongly believe that the immunological profile of the blood in patients with GBM represents a signature of the tumor, which may be used for critical objectives, including patient stratification, early diagnosis and prediction of immunotherapy efficacy. As the progression of GBM is associated with the mobilization and recruitment of peripheral monocytic cells to the tumor site, the analysis of the transcriptional heterogeneity of the circulating immune monocytic populations at single-cell resolution will enable the identification of a biomarker signature, which could be used in personalized patient management. Moreover, changes to this baseline immune profile after immunotherapy approaches, may hold valuable information to monitor and predict the patients' response towards immune treatments.
|Effective start/end date||1/01/21 → 31/12/22|
- Personalised Medicine Consortium (PMC): €50,000.00
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