124: Immunotolerance-inducing IDO-1 and Th1-cytokines are upregulated in subcutaneous panniculitis-like T-cell lymphoma; signs of an immunosuppressive microenvironment

Abstract

Aims Subcutaneous panniculitis-like T cell lymphomas represent a rare and difficult to diagnose entity of cutaneous T cell lymphomas. SPTL affects predominantly young adults and presents with multifocal subcutaneous nodules and frequently associated autoimmune features. The pathogenesis of SPTL is not completely understood. The aim of this study is to unravel molecular pathways critical to the pathogenesis for the first time. Methods We analyzed 23 skin samples from 20 newly diagnosed SPTL patients and relevant control samples of adipose and non-malignant panniculitis tissue by using gene expression microarray, quantitative PCR, and two-colour immunohistochemistry. Results Interestingly, indoleamine 2,3-dioxygenase ( IDO-1 ), an immunotolerance-inducing enzyme, was among the most highly overexpressed genes in all comparisons. The expression of Th1-specific cytokines, known to be associated with autoimmune inflammation (i.e. IFNG, CXCR3, CXCL9, CXCL10, CXCL11, and CCL5 ), were also significantly increased. Confirmed with immunohistochemistry, the morphologically malignant lymphocytes expressed CXCR3 and CXCL9. IDO-1 expression was found both in some morphologically malignant lymphocytes rimming the adipocytes and in surrounding CD11c − CD68 − cells but not in CD11c + dendritic cells in the microenvironment. The proportion of FoxP3 + cells in SPTL exceeded that in the panniculitis samples. Conclusions Our results indicate that the upregulation of the tolerogenic IDO-1 together with the upregulation of IFNG, CXCR3 ligands, and CCL5 features SPTL lesions. We anticipate that the IFNG-inducible IDO-1 expression contributes to the formation of an immunosuppressive microenvironment, favourable for the malignant T cells. This study provides a relevant molecular basis for further studies exploring novel therapeutic means for subcutaneous T cell lymphoma.