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.
Highlights
Fatal outcome in melanoma patients mostly results from occurrence of distant metastases, which are usually preceded by lymph node metastases [23,29]
It has previously been shown that melanomas can elicit an immune response [15,17] and that tumour cells can effectively be eradicated in vivo by cytotoxic activity of MHC class I restricted CD8+ Granzyme B+ (GrB+) T-cells [1]
Thirty-five patients were free of disease at the time of last follow-up, while one patient in the Sentinel Lymph Node (SLN)-positive group died of a disease-unrelated cause and four patients had developed distant metastases resulting in death in two of these patients
Summary
Fatal outcome in melanoma patients mostly results from occurrence of distant metastases, which are usually preceded by lymph node metastases [23,29]. Target cell killing by cytotoxic T-cells (CTLs) requires the help of CD4+ T-helper (Th) cells [4,12] and is negatively regulated by suppressive regulatory T-lymphocytes. These suppressive T-lymphocytes express the FoxP3 transcription factor, which we used in this study as a marker for detection of suppressive T-lymphocytes [9,30]. 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
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