Of the NHL, half are diffuse large B-cell lymphomas, followed in prevalence by follicular lymphomas, marginal zone lymphomas, Burkitt’s lymphomas, and mediastinal lymphomas. They most frequently originate from B cells, and the two main groups of B-cell lymphomas, B-cell non-Hodgkin lymphomas (NHL) and Hodgkin lymphomas, account, respectively, for about 80% and 15% of all lymphomas. Lymphomas are highly heterogeneous diseases, varying by both the type of malignant cell and the tumor location. We posit that these basic preclinical investigations will open up new and promising approaches to designing better therapies. Exploring the advantages and limitations of immunocompetent versus immunodeficient models improves our understanding of the molecular and cellular mechanisms of tumor genesis and development as well as the fundamental processes governing the interaction of tumors and their host tissues. These data allow us to understand the role of the immune system in the fight against tumors. Here, we summarize the cell lines and murine models used to study lymphomagenesis, the lymphoma microenvironment, and the efficacy of new therapies. The limited accessibility of biopsies, the heterogeneity among patients, and the subtypes of lymphomas have necessitated the development of animal models to decipher immune escape mechanisms and design new therapies. Human B-cell lymphomas, the fourth most common hematologic malignancy, are currently the subject of extensive research.
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