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Prognostic role of tumour-associated macrophages and regulatory T cells in EBV-positive and EBV-negative nasopharyngeal carcinoma.
J Clin Pathol 2018; 71(3):267-274JC

Abstract

AIMS

Tumour-associated macrophages (TAMs) and regulatory T cells (Tregs) form a special niche supporting tumour progression, and both correlate with worse survival in head and neck cancers. However, the prognostic role of TAM and Tregs in nasopharyngeal carcinoma (NPC) is still unknown. Therefore, we determined differences in TAMs and Tregs in different NPC subtypes, and their prognostic significance.

METHODS

Tissue of 91 NPCs was assessed for TAMs and Tregs by determination of CD68, CD163, CD206 and FOXP3 expression in the tumour microenvironment. Clinicopathological correlations were assessed using Pearson X2 test, Fisher's exact test, analysis of variance and Mann-Whitney U test. Survival was analysed using Kaplan-Meier curves and Cox regression.

RESULTS

CD68 and FOXP3 counts were higher in Epstein-Barr virus (EBV)-positive NPC, while CD68-/FOXP3-, CD163+/FOXP3- and CD206+/FOXP3- infiltrates were more common in EBV-negative NPC. In the whole NPC group, CD68-/FOXP3- correlated with worse overall survival (OS), and after multivariate analysis high FOXP3 count showed better OS (HR 0.352, 95% CI 0.128 to 0.968). No difference in M2 counts existed between EBV-positive and negative NPC.

CONCLUSIONS

FOXP3, a Treg marker, seems to be an independent prognostic factor for better OS in the whole NPC group. Therefore, immune-based therapies targeting Tregs should be carefully evaluated. M2 spectrum macrophages are probably more prominent in EBV-negative NPC with also functional differences compared with EBV-positive NPC.

Authors+Show Affiliations

Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.Department of Pathology, Core facility Molecular pathology and Biobanking, Netherlands Cancer Institute Antoni van Leeuwenhoek, Amsterdam, The Netherlands.Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands.Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28877959

Citation

Ooft, Marc L., et al. "Prognostic Role of Tumour-associated Macrophages and Regulatory T Cells in EBV-positive and EBV-negative Nasopharyngeal Carcinoma." Journal of Clinical Pathology, vol. 71, no. 3, 2018, pp. 267-274.
Ooft ML, van Ipenburg JA, Sanders ME, et al. Prognostic role of tumour-associated macrophages and regulatory T cells in EBV-positive and EBV-negative nasopharyngeal carcinoma. J Clin Pathol. 2018;71(3):267-274.
Ooft, M. L., van Ipenburg, J. A., Sanders, M. E., Kranendonk, M., Hofland, I., de Bree, R., ... Willems, S. M. (2018). Prognostic role of tumour-associated macrophages and regulatory T cells in EBV-positive and EBV-negative nasopharyngeal carcinoma. Journal of Clinical Pathology, 71(3), pp. 267-274. doi:10.1136/jclinpath-2017-204664.
Ooft ML, et al. Prognostic Role of Tumour-associated Macrophages and Regulatory T Cells in EBV-positive and EBV-negative Nasopharyngeal Carcinoma. J Clin Pathol. 2018;71(3):267-274. PubMed PMID: 28877959.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prognostic role of tumour-associated macrophages and regulatory T cells in EBV-positive and EBV-negative nasopharyngeal carcinoma. AU - Ooft,Marc L, AU - van Ipenburg,Jolique A, AU - Sanders,Maxime E, AU - Kranendonk,Mariette, AU - Hofland,Ingrid, AU - de Bree,Remco, AU - Koljenović,Senada, AU - Willems,Stefan M, Y1 - 2017/09/06/ PY - 2017/07/06/received PY - 2017/08/03/revised PY - 2017/08/04/accepted PY - 2017/9/8/pubmed PY - 2018/3/21/medline PY - 2017/9/8/entrez KW - head and neck cancer KW - immunohistochemistry KW - immunopathology KW - oncology SP - 267 EP - 274 JF - Journal of clinical pathology JO - J. Clin. Pathol. VL - 71 IS - 3 N2 - AIMS: Tumour-associated macrophages (TAMs) and regulatory T cells (Tregs) form a special niche supporting tumour progression, and both correlate with worse survival in head and neck cancers. However, the prognostic role of TAM and Tregs in nasopharyngeal carcinoma (NPC) is still unknown. Therefore, we determined differences in TAMs and Tregs in different NPC subtypes, and their prognostic significance. METHODS: Tissue of 91 NPCs was assessed for TAMs and Tregs by determination of CD68, CD163, CD206 and FOXP3 expression in the tumour microenvironment. Clinicopathological correlations were assessed using Pearson X2 test, Fisher's exact test, analysis of variance and Mann-Whitney U test. Survival was analysed using Kaplan-Meier curves and Cox regression. RESULTS: CD68 and FOXP3 counts were higher in Epstein-Barr virus (EBV)-positive NPC, while CD68-/FOXP3-, CD163+/FOXP3- and CD206+/FOXP3- infiltrates were more common in EBV-negative NPC. In the whole NPC group, CD68-/FOXP3- correlated with worse overall survival (OS), and after multivariate analysis high FOXP3 count showed better OS (HR 0.352, 95% CI 0.128 to 0.968). No difference in M2 counts existed between EBV-positive and negative NPC. CONCLUSIONS: FOXP3, a Treg marker, seems to be an independent prognostic factor for better OS in the whole NPC group. Therefore, immune-based therapies targeting Tregs should be carefully evaluated. M2 spectrum macrophages are probably more prominent in EBV-negative NPC with also functional differences compared with EBV-positive NPC. SN - 1472-4146 UR - https://www.unboundmedicine.com/medline/citation/28877959/Prognostic_role_of_tumour_associated_macrophages_and_regulatory_T_cells_in_EBV_positive_and_EBV_negative_nasopharyngeal_carcinoma_ L2 - http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=28877959 DB - PRIME DP - Unbound Medicine ER -