TY - JOUR
T1 - The comparable tumour microenvironment in sporadic and NF2-schwannomatosis vestibular schwannoma
AU - Gregory, Grace
AU - Jones, Adam Paul
AU - Haley, Michael
AU - Hoyle, Christopher
AU - Zeef, Leo
AU - Lin, I-Hsuan
AU - Coope, David
AU - King, Andrew
AU - Evans, D Gareth
AU - Paszek, Pawel
AU - Couper, Kevin
AU - Brough, David
AU - Pathmanaban, Omar
PY - 2023/6/13
Y1 - 2023/6/13
N2 - Bilateral vestibular schwannoma are the hallmark of NF2-related schwannomatosis, a rare tumour predisposition syndrome associated with a lifetime of surgical interventions, radiotherapy, and off-label use of the anti-angiogenic drug bevacizumab. Unilateral vestibular schwannoma develop sporadically in non-NF2-schwannomatosis patients for which there are no drug treatment options available. Tumour-infiltrating immune cells such as macrophages and T-cells correlate with increased vestibular schwannoma growth, which is suggested to be similar in sporadic and NF2-schwannomatosis-related tumours. However, differences between NF2-schwannomatosis and the more common sporadic disease include NF2-schwannomatosis patients presenting an increased number of tumours, multiple tumour types, and younger age at diagnosis. A comparison of the tumour microenvironment in sporadic and NF2-schwannomatosis tumours is therefore required to underpin development of immunotherapeutic targets, identify the possibility of extrapolating ex vivo data from sporadic vestibular schwannoma to NF2-schwannomatosis, and help inform clinical trial design with the feasibility of co-recruiting sporadic and NF2-schwannomatosis patients. This study drew together bulk transcriptomic data from three published Affymetrix microarray datasets to compare the gene expression profiles of sporadic and NF2-schwannomatosis vestibular schwannoma, and subsequently deconvolved to predict the abundances of distinct tumour immune microenvironment populations. Data were validated using quantitative PCR and Hyperion imaging mass cytometry. Comparative bioinformatic analyses revealed close similarities in NF2-schwannomatosis and sporadic vestibular schwannoma tumours across the three datasets. Significant inflammatory markers and signalling pathways were closely matched in NF2-schwannomatosis and sporadic vestibular schwannoma, relating to the proliferation of macrophages, angiogenesis, and inflammation. Bulk transcriptomic and imaging mass cytometry data identified macrophages as the most abundant immune population in vestibular schwannoma, comprising a third of the cell mass in both NF2-schwannomatosis and sporadic tumours. Importantly, there were no robust significant differences in signalling pathways, gene expression, cell-type abundance, or imaging mass cytometry staining between NF2-schwannomatosis and sporadic vestibular schwannoma. These data indicate strong similarities in the tumour immune microenvironment of NF2-schwannomatosis and sporadic vestibular schwannoma.
AB - Bilateral vestibular schwannoma are the hallmark of NF2-related schwannomatosis, a rare tumour predisposition syndrome associated with a lifetime of surgical interventions, radiotherapy, and off-label use of the anti-angiogenic drug bevacizumab. Unilateral vestibular schwannoma develop sporadically in non-NF2-schwannomatosis patients for which there are no drug treatment options available. Tumour-infiltrating immune cells such as macrophages and T-cells correlate with increased vestibular schwannoma growth, which is suggested to be similar in sporadic and NF2-schwannomatosis-related tumours. However, differences between NF2-schwannomatosis and the more common sporadic disease include NF2-schwannomatosis patients presenting an increased number of tumours, multiple tumour types, and younger age at diagnosis. A comparison of the tumour microenvironment in sporadic and NF2-schwannomatosis tumours is therefore required to underpin development of immunotherapeutic targets, identify the possibility of extrapolating ex vivo data from sporadic vestibular schwannoma to NF2-schwannomatosis, and help inform clinical trial design with the feasibility of co-recruiting sporadic and NF2-schwannomatosis patients. This study drew together bulk transcriptomic data from three published Affymetrix microarray datasets to compare the gene expression profiles of sporadic and NF2-schwannomatosis vestibular schwannoma, and subsequently deconvolved to predict the abundances of distinct tumour immune microenvironment populations. Data were validated using quantitative PCR and Hyperion imaging mass cytometry. Comparative bioinformatic analyses revealed close similarities in NF2-schwannomatosis and sporadic vestibular schwannoma tumours across the three datasets. Significant inflammatory markers and signalling pathways were closely matched in NF2-schwannomatosis and sporadic vestibular schwannoma, relating to the proliferation of macrophages, angiogenesis, and inflammation. Bulk transcriptomic and imaging mass cytometry data identified macrophages as the most abundant immune population in vestibular schwannoma, comprising a third of the cell mass in both NF2-schwannomatosis and sporadic tumours. Importantly, there were no robust significant differences in signalling pathways, gene expression, cell-type abundance, or imaging mass cytometry staining between NF2-schwannomatosis and sporadic vestibular schwannoma. These data indicate strong similarities in the tumour immune microenvironment of NF2-schwannomatosis and sporadic vestibular schwannoma.
KW - Tumour microenvironment
KW - vestibular schwannoma
KW - tumour-associated macrophages
KW - NF2 schwannomatosis
KW - NF2
M3 - Article
SN - 2632-1297
JO - Brain Communications
JF - Brain Communications
ER -