INTERACTIONS BETWEEN HEPACAM AND CD137 IN HODGKIN REED-STERNBERG CELLS ENHANCE LEUKOCYTES RECRUITMENT

Abstract

In Hodgkin Lymphoma, CD137 has been found to be involved in aiding human Hodgkin and Reed-Sternberg (HRS) cells in escape from immune surveillance by T cells inactivation. In this research project, hepaCAM (a cell adhesion molecule belonging to the immunoglobulin superfamily) was serendipitously found to be expressed on CD137-expressing HRS cell lines. Expression and co-localisation of hepaCAM in CD137-expressing HRS cells were found to be CD137-dependent using Western blot, confocal microscopy and flow cytometry. Physical interactions between hepaCAM and CD137 were confirmed by co-immunoprecipitation methods. CD137 may act as an escort molecule for hepaCAM and/or affect the expression of hepaCAM protein via CD137 signalling pathways. In addition, hepaCAM was found to be involved in attachment of HRS cells to PBMCs using cell adhesion assays and hepaCAM blocking antibodies. Using confocal microscopy, hepaCAM-mediated attraction of PBMCs to HRS cell spheroids were observed. In conclusion, CD137-dependent expression of hepaCAM on HRS cells may serve to attract PBMCs to the tumor microenvironment for subsequent inactivation.