Inflammatory cell infiltrates in advanced metastatic uveal melanoma

Publication date: Available online 24 June 2017
Source:Human Pathology
Author(s): Yamini Krishna, Conni McCarthy, Helen Kalirai, Sarah E. Coupland
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 tumour-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 (mAbs) 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 Abs against CD3 (pan-lymphocyte marker), CD4 (T-helper cells) and CD8 (T-cytotoxic cells). CD68+ and CD163+ TAMs were seen within the tumour in all 35 specimens; their density was ‘moderate’ in 50% of cases, ‘few’ in 43% and the majority showed an ‘indeterminate’ phenotype. CD3+ TILs were noted both within mUMs and surrounding the tumour. Of these CD8+ TILs were ‘few’ in number within mUM but were predominantly seen peri-tumourally at the tumour/normal liver interface, whilst CD4+ TILs showed a high perivascular density within mUM. CD68+ and CD163+ TAMs of ‘indeterminate’ morphology were observed in mUM, suggesting a tendency towards the pro-tumourigenic M2-phenotype. CD4+ TILs were seen within the mUM, whereas CD8+ TILs tended to be peri-tumoural. The biological and functional roles of inflammatory cells in mUM requires further investigation, to determine if they represent potential targets for future therapies in mUM.



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