Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas

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Maliniemi , P , Laukkanen , K , Vakeva , L , Dettmer , K , Lipsanen , T , Jeskanen , L , Bessede , A , Oefner , P J , Kadin , M E & Ranki , A 2017 , ' Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas ' , OncoImmunology , vol. 6 , no. 3 . https://doi.org/10.1080/2162402X.2016.1273310

Title: Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas
Author: Maliniemi, Pilvi; Laukkanen, Kirsi; Vakeva, Liisa; Dettmer, Katja; Lipsanen, Tuomas; Jeskanen, Leila; Bessede, Alban; Oefner, Peter J.; Kadin, Marshall E.; Ranki, Annamari
Other contributor: University of Helsinki, Department of Dermatology, Allergology and Venereology
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Department of Dermatology, Allergology and Venereology
University of Helsinki, Clinicum



Date: 2017
Language: eng
Number of pages: 10
Belongs to series: OncoImmunology
ISSN: 2162-402X
DOI: https://doi.org/10.1080/2162402X.2016.1273310
URI: http://hdl.handle.net/10138/187416
Abstract: Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three CTCL cell lines also were studied. Expression of both IDO1 and TDO was upregulated in CTCL. In MF specimens and in the MF cell line MyLa2000, IDO1 expression exceeded that of TDO, whereas the opposite was true for LyP, ALCL, and corresponding Mac1/2A cell lines. The spectrum of IDO1-expressing cell types differed among CTCL subtypes and was reflected in the clinical behavior. In MF, SPTCL, and LyP, IDO1 was expressed by malignant cells and by CD33(+) myeloid-derived suppressor cells, whereas in SPTCL CD163(+) tumor-associated macrophages also expressed IDO1. Significantly elevated serum KYN/Trp ratios were found in patients with advanced stages of MF. Epacadostat, an IDO1 inhibitor, induced a clear decrease in KYN concentration in cell culture. These results show the importance of IDO1/TDO-induced immunosuppression in CTCL and emphasize its role as a new therapeutic target.
Subject: Cutaneous T-cell lymphoma
immunosuppressive
microenvironment
indoleamine 2,3-dioxygenase1
kynurenine
tryptophan
2,3-dioxygenase
INDOLEAMINE 2,3-DIOXYGENASE 1
TUMORAL IMMUNE RESISTANCE
CANCER-IMMUNOTHERAPY
HODGKIN-LYMPHOMA
EXPRESSION
PAPULOSIS
INFLAMMATION
INHIBITION
DISEASE
PROTEIN
3122 Cancers
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