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dc.contributor.authorFhu, C.W.*
dc.contributor.authorGraham, Anne M*
dc.contributor.authorYap, C.T.*
dc.contributor.authorAl-Salam, S.*
dc.contributor.authorCastella, A.*
dc.contributor.authorChong, S.M.*
dc.contributor.authorLim, Yaw-Chyn*
dc.date.accessioned2016-11-21T15:56:38Z
dc.date.available2016-11-21T15:56:38Z
dc.date.issued2014
dc.identifier.citationFhu CW, Graham AM, Yap CT et al (2014) Reed-Sternberg cell-derived lymphotoxin-a activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma. Blood. 124(19): 2973-2982.
dc.identifier.urihttp://hdl.handle.net/10454/10454
dc.descriptionNo
dc.description.abstractIt is known that cells within the inflammatory background in classical Hodgkin lymphoma (cHL) provide signals essential for the continual survival of the neoplastic Hodgkin and Reed-Sternberg (HRS) cells. However, the mechanisms underlying the recruitment of this inflammatory infiltrate into the involved lymph nodes are less well understood. In this study, we show in vitro that HRS cells secrete lymphotoxin-α (LTα) which acts on endothelial cells to upregulate the expression of adhesion molecules that are important for T cell recruitment. LTα also enhances the expression of hyaluronan which preferentially contributes to the recruitment of CD4+ CD45RA+ naïve T cells under in vitro defined flow conditions. Enhanced expression of LTα in HRS cells and tissue stroma; and hyaluronan on endothelial cells are readily detected in involved lymph nodes from cHL patients. Our study also shows that although NF-κB and AP-1 are involved, the cyclooxygenase (COX) pathway is the dominant regulator of LTα production in HRS cells. Using pharmacological inhibitors, our data suggest that activity of COX1, but not of COX2, directly regulates the expression of nuclear c-Fos in HRS cells. Our findings suggest that HRS cell-derived LTα is an important mediator that contributes to T cell recruitment into lesional lymph nodes in cHL.
dc.subjectHodgkin lymphoma; Hodkin and Reed-Sternberg cells; cHL; HRS
dc.titleReed-Sternberg cell-derived lymphotoxin-a activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma
dc.status.refereedYes
dc.typeArticle
dc.type.versionNo full-text available in the repository
dc.identifier.doihttps://doi.org/10.1182/blood-2014-05-576140


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