Investigating the inhibitory effects of secreted proteins on macrophage in glioblastoma

Cancer is one of the major causes for the mortality in the whole world and among the cancers, glioblastoma is the most common and aggressive form of malignant brain tumours, especially in the adults. The complex tumour microenvironment of glioblastoma contributes to immune suppression and inhibition of T cell activity through secreted immuno-suppressive proteins and cytokines, dysfunction of immune cells and upregulation of immune checkpoint molecules. Macrophages are the most populous non neoplastic cells in glioblastoma microenvironment, which is a part of the innate immune response and are involved in immune suppression, tumour growth, invasion, and metastasis. The glioblastoma secretions to the microenvironment were studied using conditioned media and the day 3 with higher protein concentration were considered for studying the phagocytic activity and antigen presentation marker expression. The proteins present in the conditioned medium which were derived from these glioblastoma cell lines exert an inhibitory effect on macrophage phagocytosis. The transition from monocyte to macrophages and analysed the antigen presentation markers on monocytes and macrophages and antigen presentation marker HLA-DR had downregulated and the co-stimulatory molecule CD86 got upregulated in the presence of conditioned media suggests secretions from glioblastoma have inhibitory effect on monocytes, macrophages and the LPS stimulated M1 macrophages. Previous studies using mass spectrometry had revealed that out of 59 glioblastoma samples, 58 showed Galectin-1 as commonly secreted protein and galectin-1 was accumulated near T cells which were present around the blood vessels in glioblastoma samples. The galectin-1 secretion was regulated by IFN-ϒ, which might be from activated T cells. Along with this, the PDL-1 and galectin-9, the immune checkpoint molecules expressed on human brain endothelial cells were studied in the presence of conditioned media and IFN-ϒ. The PDL-1 was upregulated on IFN-ϒ treated conditioned media, and galectin-9 upregulated upon IFN-ϒ and the conditioned media. The immune checkpoint molecules upregulation from IFN-ϒ and conditioned media gives insight to the immune suppression in glioblastoma.

Name dc:type.qualificationname

MPhil

Level dc:type.qualificationlevel

Masters

Grantor dc:publisher.institution

University of Wolverhampton

Year dc:date.issued

2025

Author dc:creator

• Varghese, Joel

Advisor dc:contributor.advisor

• Attridge, Kesley

• cancer
• immunology
• glioblastoma
• monocytes
• macrophages
• phagocytosis
• galectin
• immune checkpoint molecules

Licence

• https://wlv.openrepository.com/bitstreams/f494e542-08bd-4cba-9dc1-2467d06a8a3f/download