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Peritumoral indoleamine 2,3-dioxygenase expression in melanoma : an early marker of resistance to immune control?

INES CHEVOLET (UGent) , Reinhart Speeckaert (UGent) , Marc Haspeslagh (UGent) , Bart Neyns, VIBEKE KRUSE (UGent) , Max Schreuer (UGent) , Mireille Van Gele (UGent) , Nanja van Geel (UGent) and Lieve Brochez (UGent)
(2014) BRITISH JOURNAL OF DERMATOLOGY. 171(5). p.987-995
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Abstract
Background: Indoleamine 2,3-dioxygenase (IDO) is an emerging immunomodulating factor in cancer. IDO expression in tumour-negative sentinel lymph nodes (SLNs) 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 (PMs), SLNs and metastases. Methods: In 120 patients with melanoma, PMs with corresponding SLNs (n = 85) and metastases (n = 18) were analysed by immunohistochemical staining for IDO and FoxP3. Tumour-infiltrating lymphocytes (TILs) were scored. IDO expression in stimulated peripheral blood mononuclear cells (PBMCs) 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 CD8+ lymphocytes (P = 0.01) and TILs (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 PBMCs 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.
Keywords
Melanoma

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Chicago
CHEVOLET, INES, Reinhart Speeckaert, Marc Haspeslagh, Bart Neyns, VIBEKE KRUSE, Max Schreuer, Mireille Van Gele, Nanja van Geel, and Lieve Brochez. 2014. “Peritumoral Indoleamine 2,3-dioxygenase Expression in Melanoma : an Early Marker of Resistance to Immune Control?” British Journal of Dermatology 171 (5): 987–995.
APA
CHEVOLET, I., Speeckaert, R., Haspeslagh, M., Neyns, B., KRUSE, V., Schreuer, M., Van Gele, M., et al. (2014). Peritumoral indoleamine 2,3-dioxygenase expression in melanoma : an early marker of resistance to immune control? BRITISH JOURNAL OF DERMATOLOGY, 171(5), 987–995.
Vancouver
1.
CHEVOLET I, Speeckaert R, Haspeslagh M, Neyns B, KRUSE V, Schreuer M, et al. Peritumoral indoleamine 2,3-dioxygenase expression in melanoma : an early marker of resistance to immune control? BRITISH JOURNAL OF DERMATOLOGY. 2014;171(5):987–95.
MLA
CHEVOLET, INES, Reinhart Speeckaert, Marc Haspeslagh, et al. “Peritumoral Indoleamine 2,3-dioxygenase Expression in Melanoma : an Early Marker of Resistance to Immune Control?” BRITISH JOURNAL OF DERMATOLOGY 171.5 (2014): 987–995. Print.
@article{5975934,
  abstract     = {Background: Indoleamine 2,3-dioxygenase (IDO) is an emerging immunomodulating factor in cancer. IDO expression in tumour-negative sentinel lymph nodes (SLNs) 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 (PMs), SLNs and metastases.
Methods: In 120 patients with melanoma, PMs with corresponding SLNs (n = 85) and metastases (n = 18) were analysed by immunohistochemical staining for IDO and FoxP3. Tumour-infiltrating lymphocytes (TILs) were scored. IDO expression in stimulated peripheral blood mononuclear cells (PBMCs) 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 {\textlangle} 0.001) and metastatic melanoma (P {\textlangle} 0.05). Sentinel IDO positivity was inversely correlated with CD8+ lymphocytes (P = 0.01) and TILs (P = 0.05) in PM. Both IDO expression in the sentinel (P {\textlangle} 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 PBMCs 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.},
  author       = {CHEVOLET, INES and Speeckaert, Reinhart and Haspeslagh, Marc and Neyns, Bart and KRUSE, VIBEKE and Schreuer, Max and Van Gele, Mireille and van Geel, Nanja and Brochez, Lieve},
  issn         = {0007-0963},
  journal      = {BRITISH JOURNAL OF DERMATOLOGY},
  language     = {eng},
  number       = {5},
  pages        = {987--995},
  title        = {Peritumoral indoleamine 2,3-dioxygenase expression in melanoma : an early marker of resistance to immune control?},
  url          = {http://dx.doi.org/10.1111/bjd.13100},
  volume       = {171},
  year         = {2014},
}

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