Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma.

Autor: Hung NA; Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand., Eiholzer RA; Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand., Kirs S; Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand., Zhou J; Department of Radiology, Southern District Health Board, Dunedin, New Zealand., Ward-Hartstonge K; Department of Microbiology and Immunology, Dunedin School of Medical Sciences, University of Otago, Dunedin, New Zealand., Wiles AK; Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand., Frampton CM; Department of Medicine, University of Otago, Christchurch, New Zealand., Taha A; Neurosurgery, Southern District Health Board, Dunedin, New Zealand., Royds JA; Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand., Slatter TL; Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Jazyk: angličtina
Zdroj: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2016 Mar; Vol. 29 (3), pp. 212-26. Date of Electronic Publication: 2016 Jan 15.
DOI: 10.1038/modpathol.2015.156
Abstrakt: Telomere maintenance is a hallmark of cancer and likely to be targeted in future treatments. In glioblastoma established methods of identifying telomerase and alternative lengthening of telomeres leave a significant proportion of tumors with no defined telomere maintenance mechanism. This study investigated the composition of these tumors using RNA-Seq. Glioblastomas with an indeterminate telomere maintenance mechanism had an increased immune signature compared with alternative lengthening of telomeres and telomerase-positive tumors. Immunohistochemistry for CD163 confirmed that the majority (80%) of tumors with an indeterminate telomere maintenance mechanism had a high presence of tumor-associated macrophages. The RNA-Seq and immunostaining data separated tumors with no defined telomere maintenance mechanism into three subgroups: alternative lengthening of telomeres like tumors with a high presence of tumor-associated macrophages and telomerase like tumors with a high presence of tumor-associated macrophages. The third subgroup had no increase in tumor-associated macrophages and may represent a distinct category. The presence of tumor-associated macrophages conferred a worse prognosis with reduced patient survival times (alternative lengthening of telomeres with and without macrophages P=0.0004, and telomerase with and without macrophages P=0.013). The immune signatures obtained from RNA-Seq were significantly different between telomere maintenance mechanisms. Alternative lengthening of telomeres like tumors with macrophages had increased expression of interferon-induced proteins with tetratricopeptide repeats (IFIT1-3). Telomerase-positive tumors with macrophages had increased expression of macrophage receptor with collagenous structure (MARCO), CXCL12 and sushi-repeat containing protein x-linked 2 (SRPX2). Telomerase-positive tumors with macrophages were also associated with a reduced frequency of total/near total resections (44% vs >76% for all other subtypes, P=0.014). In summary, different immune signatures are found among telomere maintenance mechanism-based subgroups in glioblastoma. The reduced extent of surgical resection of telomerase-positive tumors with macrophages suggests that some tumor-associated macrophages are more unfavorable.
Databáze: MEDLINE
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