Publication

Reed-Sternberg cell-derived lymphotoxin-a activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma

Fhu, C.W.
Yap, C.T.
Al-Salam, S.
Castella, A.
Chong, S.M.
Lim, Yaw-Chyn
Publication Date
2014
End of Embargo
Supervisor
Rights
Peer-Reviewed
Yes
Open Access status
closedAccess
Accepted for publication
Institution
Department
Awarded
Embargo end date
Additional title
Abstract
It 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.
Version
No full-text in the repository
Citation
Fhu 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.
Link to publisher’s version
Link to published version
Type
Article
Qualification name
Notes