Expression of Tim-1 in primary CNS lymphoma

Abstract

Primary central nervous system lymphoma (PCNSL) is a distinct subtype of extranodal lymphoma with aggressive clinical course and poor outcome. As increased IL-10/IL-6 ratio is recognized in the cerebrospinal fluid (CSF) of PCNSL patients, we hypothesized that PCNSL might originate from a population of B cells with high IL-10-producing capacity, an equivalent of "regulatory B cells" in mice. We intended in this study to clarify whether Tim-1, a molecule known as a marker for regulatory B cells in mice, is expressed in PCNSL. By immunohistochemical analysis, Tim-1 was shown to be positive in as high as 54.2% of PCNSL (26 of 58 samples), while it was positive in 19.1% of systemic diffuse large B-cell lymphoma (DLBCL) samples (17 of 89 samples; P < 0.001). Tim-1 expression positively correlated with IL-10 expression in PCNSL (Cramer's V = 0.55, P < 0.001), and forced expression of Tim-1 in a PCNSL cell line resulted in increased IL-10 secretion, suggesting that Tim-1 is functionally linked with IL-10 production in PCNSL. Moreover, soluble Tim-1 was detectable in the CSF of PCNSL patients, and was suggested to parallel disease activity. In summary, PCNSL is characterized by frequent Tim-1 expression, and its soluble form in CSF may become a useful biomarker for PCNSL.