Expression of cancer-testis antigens in late stage melanoma is associated with high FoxP3 expression in tumour infiltrating lymphocytes in early stage disease

Abstract

Background FoxP3 is a marker of regulatory T lymphocytes (Tregs). Cancer-Testis Antigens (CTA) are immunogenic molecules with restricted expression to tumour and immune-privileged sites, and serve as potential targets for anti-cancer immunity. As immune recognition, surveillance and editing is dynamic, our aim was to observe for an association between CTA expression and Tregs between early (stage I/II) and late (stage III/IV) stage melanoma. Methods Immunohistochemistry of 22 patients with paired stage I/II and stage III/IV melanoma, and non-paired 103 stage I/II and 257 stage III/IV melanomas was performed for FoxP3 (in tumour infiltrating lymphocytes; TILs) and for a panel of CTAs (MAGE-A1, MAGE-A3/A4, MAGE-C1 and NY-ESO-1). Results and Conclusion In the paired tumours, an increase in the numbers of CTA expressed with advanced disease was associated with increased frequency of FoxP3 positive TILs in primary tumour ( p = 0.03). Direct association between CTA expression and increased frequency of Tregs was only observed in late stage melanoma ( p = 0.03). Discussion The presence of FoxP3 TILs may be a marker for in situ immunosuppression. The emergence of immunogenic CTA expression in this situation may reflect this, however, CTA expression and in situ immunosuppression both mark cancer progression and any link between these remains to be clearly established.