Indoleamine 2,3-Dioxygenase Expression in Primary Cutaneous Melanoma Correlates with Breslow Thickness and Is of Significant Prognostic Value for Progression-Free Survival

Abstract

The enzyme indoleamine 2,3-dioxygenase (IDO) is emerging as a facilitator of cancer development through its effects on cancer-associated inflammation. Recent studies report a significant improvement of the response rates in melanoma patients to PD-1 antibodies when IDO inhibitors were added to the regimen. Data on IDO expression in primary human melanomas are, however, incomplete and conflicting. Here, we show that the level of IDO expression in primary human melanoma cells significantly correlates with Breslow thickness (P=0.003), the presence of tumor-infiltrating lymphocytes (P= 0.029), and the intensity of the peritumoral inflammatory infiltrate (P= 0.001). The expression of IDO in melanoma cells predicted independently of Breslow thickness and tumor stage (P= 0.04). We further show that CD11c+ dendritic cells and CD68+ macrophages in the microenvironment of melanomas express IDO. The level of IDO expression in antigen-presenting cells correlated positively to peritumoral inflammation (P= 0.001) but not to tumor-infiltrating lymphocytes. Significant negative correlation with progression-free survival was found for patients for whom antigen-presenting cells were very strongly IDO positive. These results suggest that IDO induction within melanoma cells may directly reflect tumor progression, whereas IDO in antigen-presenting cells may determine immune surveillance with impact on local and systemic tolerance.