Absence of Granzyme B Positive Tumour-Infiltrating Lymphocytes in Primary Melanoma Excisional Biopsies is Strongly Associated with the Presence of Sentinel Lymph Node Metastasis

Abstract

Background: Sentinel Lymph Node (SLN) status is strongly related to clinical outcome in melanoma patients. In this study we investigated the possible association between the presence of activated and/or suppressive Tumour Infiltrating Lymphocytes (TILs) and SLN status in clinically stage I/II melanoma patients.

Methods: Diagnostic primary melanoma samples from 20 patients with a sentinel lymph node metastasis were compared to melanoma samples from 20 patients with a negative sentinel lymph node, who were matched for gender, age and Breslow thickness. Presence of activated Granzyme B positive (GrB⁺) TILs, presence of suppressive (FoxP3⁺) TILs and MHC class I antigen expression on tumour cells were analysed by immunohistochemistry.

Results: FoxP3 and MHC-I expression had no direct bearing on the presence of melanoma metastases in the SLN. Whereas the presence of activated GrB⁺ TILs in the primary melanoma had no predictive value for SLN status either, their absence was strongly associated with the presence of metastasis in the SLN (p=0.001). While both GrB⁺ and FoxP3⁺ TILs could be detected in SLN metastases, a majority did not display MHC-I expression.

Conclusions: These data support a role for cytotoxic T cells in the prevention of early metastasis of melanoma to the draining lymph nodes.