We previously reported a strong IL4I1 gene expression in primary mediastinal
B-cell lymphoma (PMBL) and recently identified the
protein as a secreted
L-phenylalanine oxidase, physiologically expressed by myeloid cells, which inhibits T-cell proliferation in vitro. Here, we analyzed the pattern of IL4I1
protein expression in 315 human lymphoid and non-lymphoid
malignancies. Besides PMBL, IL4I1 expression in
tumors was very frequent. IL4I1 was detected in tumor-associated macrophages from most of the
tumors and in neoplastic cells from
follicular lymphoma, classic and nodular lymphocyte predominant Hodgkin
lymphomas and
small lymphocytic lymphoma, three of which are germinal center derived. IL4I1-positive
tumor cells were also detected in rare cases of solid
cancers, mainly
mesothelioma. The enzymatic activity paralleled
protein expression, suggesting that IL4I1 is functional in vivo. Depending on the
tumor type, IL4I1 may impact on different infiltrating lymphocyte populations with consequences on
tumor evolution. In the particular case of
follicular lymphoma cells, which are susceptible to antitumor cytotoxic T cells killing but depend on interactions with local T helper cells for survival, a high level of IL4I1 expression seems associated with the absence of bone marrow involvement and a better outcome. These findings plead for an evaluation of IL4I1 as a prognosis factor.