Inflammatory cell infiltrates in metastatic uveal melanoma

Purpose Current treatments for metastatic UM (MUM) are very limited and rarely prolong patient survival. Immunotherapy trials for MUM are few, and to date have only demonstrated marginal success. High densities of tumour associated macrophages (TAMs) and infiltrating T lymphocytes (TILs) in primary UM are associated with a poor prognosis. There is little known about the immunomodulatory/microenvironment of MUM. Our aim was to examine the presence and distribution of TAMs and TILs in MUM within the liver. Methods Whole tissue sections of liver MUM ( n  =   16) were examined by immunohistochemistry. For TAMs, the monoclonal antibodies (mAb) against CD68 and CD163 were used. Macrophage number and morphology were graded following the method described by Mӓkitie et al (IOVS 2001;42(7):1414–21). Number and spatial distribution of TILs were highlighted using Abs against CD3 (pan‐lymphocyte marker), CD4 (T‐helper cells) and CD8 (T‐cytotoxic/suppressor cells). Results CD68+ and CD163+ TAMs were noted within the tumour in all 16 specimens; their numbers were ‘few to moderate’ in ≥85% of cases and the majority showed an intermediate phenotype. CD3+ TILs were noted both within MUMs and surrounding the tumour, at the interface with normal liver. Of these CD8+ TILs were ‘few’ in number within MUM but were predominantly seen at the tumour/normal liver interface, whilst CD4+ TILs showed a high perivascular density within MUM. The CD4 mAb also highlighted resident Kupffer‐Stern macrophages. Conclusions CD68+ and CD163+ TAMs of intermediate morphology were observed in MUM, suggesting a tendency towards the pro‐tumourigenic M2 phenotype. CD4+ TILs were seen mainly infiltrating MUM, whereas CD8+ TILs tended to be peritumoural. The biological role of inflammatory cells in MUM requires further investigation, to determine if they represent potential targets for future therapies in MUM.