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Hum Pathol. 2017 Aug;66:159-166. doi: 10.1016/j.humpath.2017.06.005. Epub 2017 Jun 24.

Inflammatory cell infiltrates in advanced metastatic uveal melanoma.

Author information

1
Department of Cellular Pathology, Royal Liverpool University Hospital, Liverpool, L7 8XP, UK.
2
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, L7 8TX, UK.
3
Department of Cellular Pathology, Royal Liverpool University Hospital, Liverpool, L7 8XP, UK; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, L7 8TX, UK. Electronic address: s.e.coupland@liverpool.ac.uk.

Abstract

Current treatments for metastatic uveal melanoma (mUM) are limited and rarely prolong patient survival. Immunotherapy trials for mUM are few and to date have demonstrated only marginal success. High densities of tumor-associated macrophages (TAMs) and infiltrating T lymphocytes (TILs) in primary UM are associated with poor prognosis. Little is known about the immune microenvironment of mUM. Our aim was to examine the presence and distribution of TAMs and TILs in mUM within the liver. Whole-tissue sections of liver mUM (n=35) were examined by immunohistochemistry. For TAMs, monoclonal antibodies against CD68 and CD163 were used. Macrophage density and morphology were scored using previous established systems. Density and spatial distribution of TILs were highlighted using antibodies against CD3 (pan-lymphocyte marker), CD4 (T-helper cells), and CD8 (T-cytotoxic cells). CD68+ and CD163+ TAMs were seen within the tumor in all 35 specimens; their density was "moderate" in 50% of cases and "few" in 43%, and the majority showed an "indeterminate" phenotype. CD3+ TILs were noted both within mUMs and surrounding the tumor. Of these, CD8+ TILs were "few" in number within mUM but were predominantly seen peritumorally at the tumor/normal liver interface, whereas CD4+ TILs showed a high perivascular density within mUM. CD68+ and CD163+ TAMs of "indeterminate" morphology were observed in mUM, suggesting a tendency toward the protumorigenic M2 phenotype. CD4+ TILs were seen within the mUM, whereas CD8+ TILs tended to be peritumoral. The biological and functional roles of inflammatory cells in mUM require further investigation to determine if they represent potential targets for future therapies in mUM.

KEYWORDS:

Immunotherapy; Inflammation; Liver; Macrophages; Metastatic uveal melanoma; T cells

PMID:
28655639
DOI:
10.1016/j.humpath.2017.06.005
[Indexed for MEDLINE]

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