Tumor cell survival and immune escape mechanisms in classical Hodgkin lymphoma

Tumor cell survival and immune escape mechanisms in classical Hodgkin lymphomaThe nature of classical Hodgkin lymphoma (HL), a minority of tumor cells in a reactive background and loss of B cell phenotype, decides its dependence on the microenvironment for signals to contribute to survival and proliferation while at the same time trying to escape an anti-tumor response especially fired up because of the presence of Epstein Barr virus (EBV) in the tumor cells. The data in this thesis show involvement of new players in the survival of the tumor cells in HL and their escape from anti-tumor immune responses. In addition to known pathways that are aberrantly activated in the tumor cells, aberrant expression of Insulin-like growth factor-1 receptor (IGF-1R), Ephrin family members and Toll-like receptors (TLRs) might provide additional signals leading to the survival and growth of the tumor cells. Despite the oncogenic effect of IGF-1R in cell lines, IGF-1R expression in the tumor cells of primary cases predicts a favorable outcome. The wide expression of Ephrin family members both in the tumor cells and the microenvironment suggests that there is a role for the Ephrin family in the pathogenesis of HL. Similarly, the expression of TLRs by the tumor cells supports a role in HL pathogenesis, although the effect of triggering of TLRs on HL cell lines was limited.In terms of immune escape, potential mechanisms involve lack of functional antigen expressing, such as downregulation of HLA class I and II, and retention of CLIP, by loss of HLA-DM, in HLA class II molecules impairing antigen presentation in HL. In undifferentiated nasopharyngeal carcinoma, another EBV associated cancer, HLA class I and II downregulation was observed in part of the cases. The expression of HLA class II was strongly correlated to HLA-DM and HLA-DO expression, suggesting interference of HLA-DO with the function of HLA-DM, leading to expression of CLIP and impaired antigen presentation