Expression of Tim‐1 in primary CNS lymphoma

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.