In Vitro Diffuse Large B-Cell Lymphoma Cell Line Models as Tools to Investigate Novel Immunotherapeutic Strategies

SIMPLE SUMMARY: Despite a range of emerging immunotherapeutic strategies, the aggressive nature of DLBCL poses an ongoing clinical challenge. Therefore, there is a need to pursue more effective treatment modalities based on monoclonal antibodies, antibody-drug conjugates and CAR-T cell therapy. Up to now, the above-mentioned immunotherapeutic options have been extensively studied with the aid of established cell line models, which have significantly facilitated proceeding from preclinical to clinical investigations and led to improvement of DLBCL treatment. However, there are still several important challenges associated with faithful recapitulation of the aggressive nature of DLBCL. Therefore, the current review discusses means in which cell line models fulfill an essential tool leading to greater understanding DLBCL biology and development of novel immunotherapeutic strategies. ABSTRACT: Despite the high incidence of diffuse large B-cell lymphoma (DLBCL), its management constitutes an ongoing challenge. The most common DLBCL variants include activated B-cell (ABC) and germinal center B-cell-like (GCB) subtypes including DLBCL with MYC and BCL2/BCL6 rearrangements which vary among each other with sensitivity to standard rituximab (RTX)-based chemoimmunotherapy regimens and lead to distinct clinical outcomes. However, as first line therapies lead to resistance/relapse (r/r) in about half of treated patients, there is an unmet clinical need to identify novel therapeutic strategies tailored for these patients. In particular, immunotherapy constitutes an attractive option largely explored in preclinical and clinical studies. Patient-derived cell lines that model primary tumor are indispensable tools that facilitate preclinical research. The current review provides an overview of available DLBCL cell line models and their utility in designing novel immunotherapeutic strategies.