Variable indoleamine 2,3-dioxygenase expression in acral / mucosal melanoma and its possible link to immunotherapy.

Variable indoleamine 2,3-dioxygenase expression in acral / mucosal melanoma and its possible link to immunotherapy.

Publication date: Sep 11, 2019

Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although PD-L1 is a well-studied biomarker for response to anti-PD-1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3-dioxygenase (IDO) is correlated to a response to anti-CTLA-4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti-PD-1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in the Western countries. To evaluate the association of IDO and PD-L1 expression with response to anti-PD-1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti-PD-1 antibody in the perspective of IDO and PD-L1 expression levels by immunohistochemistry. Multivariate Cox regression models showed that the low expression of IDO in tumor was associated with poor progression-free survival (HR = 0.33, 95% CI = 0.13-0.81, P = 0.016), whereas PD-L1 expression on tumor was not associated with progression-free survival. Significantly lower expression of IDO in tumor was found in non-responders than in responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti-PD-1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings. This article is protected by copyright. All rights reserved.

Iga, N., Otsuka, A., Hirata, M., Kataoka, T.R., Irie, H., Nakashima, C., Matsushita, S., Uchi, H., Yamamoto, Y., Funakoshi, T., Fujisawa, Y., Yoshino, K., Fujimura, T., Hata, H., Ishida, Y., and Kabashima, K. Variable indoleamine 2,3-dioxygenase expression in acral / mucosal melanoma and its possible link to immunotherapy. 24063. 2019 Cancer Sci.

Concepts Keywords
Antibody Acral mucosal melanoma
Biomarker Expression IDO tumor
Cox Regression Therapy melanoma
Frequency Subtypes cutaneous melanomas
Immunohistochemistry Acral mucosal melanomas
Immunotherapy Immunotherapy
Japanese Medicine
Melanoma Immune system
Melanomas Organ systems
Prognosis Medical specialties
Sci Melanoma
Tumor Immune checkpoint
Checkpoint inhibitor
Ido
Pembrolizumab
Uveal melanoma

Semantics

Type Source Name
disease MESH tumor
gene UNIPROT CPOX
gene UNIPROT RXFP2
gene UNIPROT CTLA4
gene UNIPROT IDO1
gene UNIPROT RPL17
gene UNIPROT CD274
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
disease DOID mucosal melanoma

Original Article

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