Pilvi Maliniemi
University of Helsinki
Finland
Title: The immunomodulatory and prognostic role ofindoleamine-2,3-dioxygenase-1 in cutaneous T-cell lymphomas
Biography
Biography: Pilvi Maliniemi
Abstract
Indoleamine-2,3-deoxygenase (IDO-1), catabolizing tryptophan(Trp) to kynurenine (Kyn), causes an immunosuppressive microenvironment in many neoplasias. In this study we identify the IDO-expressing cell subtypes in cutaneous T-cell lymphoma (CTCL) and determine the significance of serum Kyn/Trpcatabolite levels. IDO-1 mRNA and protein expression was studied in 68 FFPE skin samples of mycosis fungoides (MF), lymphomatoidpapulosis (LyP), lichen ruberplanus (LRP), and subcutaneous panniculitic-like T cell lymphoma (SPTL), and in three CTCL cell lines. For co-expression, anti-CD33 (myeloid-derived suppressor cells, MDSC) and anti-CD163 (tumor-associated macrophages, TAM) antibodies were used. Levels of 14 Trp metabolites were measured in 69 patient and healthy control sera by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The relative expression of IDO-1 mRNA was markedly elevated in MF and LyP samples compared to LRP and also in the MF-derived cell line MyLa compared to the CD30+ CTCL lines Mac-1 and Mac-2A. Interestingly, IDO was co-expressed by CD33+ MDSCs in MF and in LyP and by the CD163+ TAMS in SPTL. The increase of IDO also associated with the eleveted level of Treg cells in LyP as 50% of the cases studied showed a moderate or strong FoxP3 expression. Serum Kyn/Tryp ratios showed significant increase in MF (p<0.05) compared with those of healthy controls and correlated with MF activity. We show that IDO is produced by the MF cell line MyLa and by CD33+ MDSCs in MF and in LyP but instead by CD163+ TAMs in SPTL. FoxP3+ Tregs, abundant in LyP, may contribute to the indolent clinical behavior. Serum Kyn/Tryp ratio in MF associates to a progressive disease behavior and may be a useful clinical indicator.