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Objectives: This study aimed to decipher a correlation between CXCL16 and CD99 expressions and to investigate the role of CXCL16 in human lymphoma cell lines and clinical samples.Methods: Cytokine antibody arrays were used to measure the differently expressed cytokines in tumor tissues.Expression of CXCL16 and CD99 was analyzed by quantitative real time-PCR (qRT-PCR) and western blot (WB),while involved pathways were assessed by WB and ELISA assays.CXCL16 expressions were investigated in 9 lymphoma cell lines (L428,RPMI-8226,KM3,Jurkat,OCI-Lyl,OCI-Ly8,OCI-Lyl0,Karpass299,Raji) as well as clinical lymphoma samples using qRT-PCR,WB and immunochemistry.Soluble CXCL16 (sCXCL16) levels were measured by ELISA and proliferation was analyzed by CCK8 proliferation assays.Results: CXCL16 was one of the up-regulated chemokines when lymphoma cells was transferred from in vitro to in vivo conditions.The increased expression and secretion of CXCL16 paralleled with decrease of mCD99L2 and was accompanied by NF-κ,B pathway activation and vice versa.CXCL16 was expressed in all nine lymphoma cell lines with the highest levels in the Hodgkin lymphoma cell line (L428),the plasma cell derived cell lines (RPMI-8226,KM3) and the T leukemia derived cell line (Jurkat).Higher levels of sCXCL16 were secreted by L428 cells,the diffuse large B cell lymphoma (DLBCL) derived cell lines (OCI-Lyl,OCI-Ly8,OCI-Lyl0) and Jurkat cells.CXCL16 was widely expressed in clinical samples of lymphoma patients with higher levels in Hodgkin lymphoma than in non-Hodgkin lymphoma.Human recombinant CXCL16 had no significant effect on L428 cell proliferation,but could stimulate CD4+T lymphocytes to proliferate.Conclusion: CXCL1 6,inversely correlated with CD99 expression in H/RS cells,is widely expressed in diverse types of lymphomas.