Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma
| Autor: | Ahmad Taha, Ramona A Eiholzer, Anna Wiles, Chris Frampton, Kirsten A Ward-Hartstonge, Jean Zhou, Noelyn Hung, Stenar Kirs, Janice A. Royds, Tania L. Slatter |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Telomerase Pathology medicine.medical_specialty Angiogenesis Blotting Western Kaplan-Meier Estimate Biology Polymerase Chain Reaction Pathology and Forensic Medicine 03 medical and health sciences Immune system medicine Humans Aged Brain Neoplasms Macrophages Cancer Middle Aged Telomere Prognosis medicine.disease Immunohistochemistry Macrophage receptor with collagenous structure 030104 developmental biology Female Glioblastoma CD163 |
| Zdroj: | Modern Pathology. 29:212-226 |
| ISSN: | 0893-3952 |
| Popis: | 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 tumorassociated 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 476% 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. Modern Pathology advance online publication, 15 January 2016; doi:10.1038/modpathol.2015.156 |
| Databáze: | OpenAIRE |
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