Immu-12. Aberrant Egfr Signaling Is Associated With Diminished Cytotoxic T-cell Infiltration in Glioblastoma Patients
Year: 2022
Type: conference-abstract
Abstract: Glioblastoma (GBM) has not benefitted from recent advances in immunotherapy compared to other solid malignancies, which suggests that a deeper understanding of the immunobiology of GBM is necessary to develop better therapeutic options. Both oncogenic signaling and evasion of immune destruction are hallmarks of cancer, contributing to tumor growth and reduced survival, respectively. Despite recent evidence in non-CNS malignancies demonstrating the importance of aberrant oncogenic signaling on shaping the tumor immune microenvironment, the impact of aberrant epidermal growth factor (EGFR) signaling – genetically altered in 60% of GBM patients - on the tumor immune microenvironment is not well characterized in GBM. To evaluate the importance of altered EGFR signaling in GBM patient samples, we performed single-cell transcriptomic analysis of primary tumor infiltrating leukocytes (TILs) from twenty-five patients which revealed aberrant EGFR signaling is associated with a unique tumor immune microenvironment in both primary and recurrent disease. Specifically, in the primary disease setting, higher infiltration of macrophages and dendritic cells, and significantly lower infiltration of T-regulatory cells was observed in EGFR altered patients compared to non-altered patients. In recurrent disease, EGFR alterations were associated with significantly diminished infiltration of activated and activated exhausted cytotoxic T-cells compared to unaltered disease. Intriguingly, differential gene expression analysis revealed that EGFR altered patients display significantly increased expression of interferon stimulated genes (ISGs) in both myeloid and lymphoid lineages, while analysis of the tumor compartment unexpectedly revealed greater expression of MHCI genes. Collectively, these data emphasize the impact of aberrant EGFR signaling on the tumor immune microenvironment composition and suggest further characterization of EGFR-immune crosstalk and mechanism is warranted in GBM.
Source: Neuro-Oncology
Authors: Marissa Pioso, Lu Sun, Nicholas Bayley, Amanda Anil, Alexander Lee, David Nathanson, Robert Prins
Institution: University of California, Los Angeles
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4308978001