Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology.

Autor: Amit M; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. mamit@mdanderson.org., Xie T; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gleber-Netto FO; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hunt PJ; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA.; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Mehta GU; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Division of Neurosurgery, House Ear Institute, Los Angeles, CA, USA., Bell D; Anatomic Pathology, Head and Neck Disease Alignment Team, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.; Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Silverman DA; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Yaman I; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Ye Y; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY, USA.; Department of Oral Maxillofacial Surgery, New York University College of Dentistry, New York, NY, USA.; Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY, USA., Burks JK; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Fuller GN; Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.; Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Gidley PW; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Nader ME; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Raza SM; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., DeMonte F; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. fdemonte@mdanderson.org.
Jazyk: angličtina
Zdroj: Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2022 Oct 04; Vol. 41 (1), pp. 292. Date of Electronic Publication: 2022 Oct 04.
DOI: 10.1186/s13046-022-02473-4
Abstrakt: 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 + , CD8 + , CD20 + , and CD68 + immune cells. RNA data indicated the upregulation of anti-viral innate immune response and T-cell senescence. K - Top Scoring Pair analysis identified 6 pairs of immunosenescence-related genes (CD38-KDR, CD22-STAT5A, APCS-CXCR6, MADCAM1-MPL, IL6-NFATC3, and CXCL2-TLR6) that had high sensitivity (100%) and specificity (78%) for identifying rapid VS progression.
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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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