Emerging Role of IL-4-Induced Gene 1 as a Prognostic Biomarker Affecting the Local T-Cell Response in Human...

Several studies have emphasized the importance of immune composition of the melanoma microenvironment for clinical outcome. The contribution of IL4I1, a phenylalanine oxidase with immunoregulatory functions, has not been yet explored. Here we studied a primary cutaneous melanoma series from stage I-III patients to investigate the association between in situ IL4I1 expression and clinical parameters or tumor-infiltrating T-cell subsets. IL4I1 was detected in 87% of tumors and was mainly expressed by tumor-associated macrophages and very rare FoxP3⁺ regulatory T cells. The proportion of IL4I1⁺ cells was higher in patients with an ulcerated melanoma or with a positive sentinel lymph node and tended to correlate with a rapid relapse and shorter overall survival. This proportion also correlated positively with the presence of regulatory T cells and negatively with the presence of cytotoxic CD8⁺ T cells. The location of IL4I1⁺ cells may also be relevant to predict prognosis, because their presence near tumor cells was associated with sentinel lymph node invasion and higher melanoma stage. Collectively, our data show that IL4I1⁺ cells shape the T-cell compartment and are associated with a higher risk of poor outcome in melanoma, supporting a key role for IL4I1 in immune evasion.