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Peritumoral indoleamine 2,3‐dioxygenase expression in melanoma: an early marker of resistance to immune control?
Author(s) -
Chevolet I.,
Speeckaert R.,
Haspeslagh M.,
Neyns B.,
Krüse V.,
Schreuer M.,
Van Gele M.,
Van Geel N.,
Brochez L.
Publication year - 2014
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.13100
Subject(s) - medicine , indoleamine 2,3 dioxygenase , melanoma , sentinel lymph node , immune system , peripheral blood mononuclear cell , foxp3 , immunohistochemistry , tumor infiltrating lymphocytes , cd8 , immunology , cancer research , pathology , cancer , breast cancer , biology , tryptophan , biochemistry , amino acid , in vitro
Summary Background Indoleamine 2,3‐dioxygenase ( IDO ) is an emerging immunomodulating factor in cancer. IDO expression in tumour‐negative sentinel lymph nodes ( SLN s) of patients with melanoma has a negative prognostic value. Objectives To analyse the expression pattern of IDO and associated immunological changes in corresponding primary melanomas ( PM s), SLN s and metastases. Methods In 120 patients with melanoma, PM s with corresponding SLN s ( n = 85) and metastases ( n = 18) were analysed by immunohistochemical staining for IDO and FoxP3. Tumour‐infiltrating lymphocytes ( TIL s) were scored. IDO expression in stimulated peripheral blood mononuclear cells ( PBMC s) was analysed in 27 patients. Results IDO expression in the sentinel node strongly correlated with endothelial IDO expression in the peritumoral stroma of the corresponding primary ( P < 0·001) and metastatic melanoma ( P < 0·05). Sentinel IDO positivity was inversely correlated with CD 8+ lymphocytes ( P = 0·01) and TIL s ( P = 0·05) in PM . Both IDO expression in the sentinel ( P < 0·01) and the PM ( P = 0·04) had a negative prognostic effect on overall survival, independent of Breslow thickness, sex, age, ulceration and sentinel invasion. IDO expression by PBMC s after stimulation with cytotoxic T‐lymphocyte antigen 4 was not correlated with sentinel IDO expression but tended to correlate with disease stage ( P = 0·04). Conclusions Endothelial IDO expression is highly consistent in primary, sentinel and metastatic tissues of patients with melanoma, indicating that immune suppression in melanoma is determined very early in the disease course. This supports that IDO expression in melanoma is a marker of antitumour immune response with an independent prognostic value.