α/β- and γ/ζ TCR+ lymphocyte infiltration in necrotising choroidal melanomas

Abstract

Aim - To detect specific tumour infiltrating T cells (TIL) carrying antigen specific MHC-I restricted receptor genes on necrotising and non-necrotising malignant melanomas and to correlate the findings with clinical data. Methods - α/β- and γ/ζ- TIL were determined by immunohistochemical staining in melanomas of patients with known follow up of more than 10 years. An antigen retrieval method was used to determine variable genes ζ1 and γ1 on TCR+ cells by an anti-TCR Vζ1 and anti-CrγM1, and of Vα and Vβ TCR+ by an anti-pan-TCR+ α/β antibody. Results - Intratumoral TIL were present in 86 of 113 (76.1%) necrotising melanomas (NMM) v 21 of 100 (21%) in non-necrotising melanomas (MM); of these, Vα/β- TCR+ cells were present in 52 of 74 (70.3%) TIL harbouring NMM v four of 21 (19%) MM; Vγ1 in 29 of 74 (39.2%) NMM v two of 21 (10%) MM; and Vζ1 in 39 of 74 (52.7%) NMM v three of 21 (14%) MM. Extratumoral lymphocytic infiltration was seen in 86 (76.1%) NMM including Vα/β TCR+ cells in 10 (11.6%) cases, v five (5%) MM cases with no Vα/β TCR+ cells detected. Vγ1 and Vζ1 TCR+ cells were not found in extratumoral infiltrates. Conclusions - In NMM, the median survival was 69.3 (range 6-237) months, 19 of 74 patients (25.7%) survived 5 years, and mortality was associated with advanced stage (p < 0.001), patient age (p < 0.023), and extent of necrosis (p < 0.048). Survival was increased with evidence of Vγ1 and Vζ1 TCR+ cells (p < 0.026).