Distinct Immune Signature Predicts Progression of Vestibular Schwannoma and Unveils a Possible Viral Etiology

Authors

Moran Amit
Tongxin Xie
Frederico O Gleber-Netto
Patrick J Hunt
Gautam U Mehta
Diana Bell
Deborah A Silverman
Ismail Yaman
Yi Ye
Jared K Burks
Gregory N Fuller
Paul W Gidley
Marc-Elie Nader
Shaan M Raza
Franco DeMonte

Publication Date

10-4-2022

Journal

Journal of Experimental & Clinical Cancer Research

Abstract

BACKGROUND: The management of sub-totally resected sporadic vestibular schwannoma (VS) may include observation, re-resection or irradiation. Identifying the optimal choice can be difficult due to the disease's variable progression rate. We aimed to define an immune signature and associated transcriptomic fingerprint characteristic of rapidly-progressing VS to elucidate the underpinnings of rapidly progressing VS and identify a prognostic model for determining rate of progression.

METHODS: We used multiplex immunofluorescence to characterize the immune microenvironment in 17 patients with sporadic VS treated with subtotal surgical resection alone. Transcriptomic analysis revealed differentially-expressed genes and dysregulated pathways when comparing rapidly-progressing VS to slowly or non-progressing VS.

RESULTS: Rapidly progressing VS was distinctly enriched in CD4

CONCLUSION: Rapid progression of residual vestibular schwannoma following subtotal surgical resection has an underlying immune etiology that may be virally originating; and despite an abundant adaptive immune response, T-cell immunosenescence may be associated with rapid progression of VS. These findings provide a rationale for clinical trials evaluating immunotherapy in patients with rapidly progressing VS.

Keywords

Cell Adhesion Molecules, Humans, Interleukin-6, Mucoproteins, Neuroma, Acoustic, Prognosis, RNA, Toll-Like Receptor 6, Tumor Microenvironment, Vestibular schwannoma, Skull base, Surgery, Immune, Viral, Progression

Comments

Supplementary Materials

PMID: 36195959