Thesis

Investigating the Role of Tumor-Associated Neutrophils (TANs) in the Suppression of T cell Function in Glioblastoma

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Glioblastoma (GBM) is known as a highly aggressive and malignant form of brain cancer. Despite
advances in understanding the genetic and molecular basis of glioblastoma, it has a poor prognosis
with a median survival rate of 9 months. The complex interplay between malignant cells and the
surrounding tumor microenvironment (TME) plays a pivotal role in tumor progression and treatment
response. However, not all of the non-malignant cells have been extensively studied in terms of their
contribution towards the TME such as tumor associated neutrophils and its relation with T-cells. We
investigated the association and role of TANs in T-cell function suppression to pave the way for novel
combinatorial therapeutic strategies for glioblastoma multiforme by co-culturing cells followed by
qRT-PCR to observe the changes in gene expression levels and IF staining to understand T-cell
activation during the co-culture. It was found that when neutrophils are co-cultured individually with
A172 cells, they suppress the aggressive MES-like GBM subtype by downregulating PDGFRA
expression. Conversely, co-culturing Jurkat T-cells individually with A172 cells reduces the expression
of genes associated with GBM aggressiveness and enhances NF1, a tumor-suppressor gene. However,
co-culturing all three cell types together abolishes T-cell-mediated suppression of pro-tumor genes,
resulting in immunosuppression. This is evidenced by increased expression of CDK4, PDGFRA, and
EGFR, decreased NF1 expression, and reduced fluorescence intensity through immunofluorescence
staining. Further experiments can be conducted including cytokine profiling and RNA sequencing
analysis to understand the pathways involved in the co-culture process.

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Availability

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Detail Information

Series Title

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Call Number

BT 24-015

Publisher

i3L, Jakarta : i3L Press., 2024

Collation

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Language

English

ISBN/ISSN

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Classification

NONE

Content Type

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Media Type

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Carrier Type

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Edition

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Subject(s)

Neutrophils
glioblastoma
tumor microenvironment
TANs
T-cells

Specific Detail Info

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Statement of Responsibility

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