Tumor Immune Microenvironment in Lymphoma: Focus on Epigenetics

SIMPLE SUMMARY: Lymphoma and other cancers have been studied by mainly focusing on malignant cells. However, research findings about the role of the tumor microenvironment in the progression and immunosuppression of cancer, particularly in lymphomas, have increased considerably in recent years, allowing for a better understanding of the disease. Consequently, epigenetic mechanisms that are implicated in the interplay between tumor cells and the different components around them, promoting the survival and progression of the tumor, have been described. This review tries to summarize the complex interplay between lymphoma tumor cells and immune cells as well as the epigenetic alterations that result from this cross-talk, aiming at contributing towards underlining the value of epigenetic modifications as new biomarkers and the use of epigenetic drugs as an interesting therapeutic option. ABSTRACT: Lymphoma is a neoplasm arising from B or T lymphocytes or natural killer cells characterized by clonal lymphoproliferation. This tumor comprises a diverse and heterogeneous group of malignancies with distinct clinical, histopathological, and molecular characteristics. Despite advances in lymphoma treatment, clinical outcomes of patients with relapsed or refractory disease remain poor. Thus, a deeper understanding of molecular pathogenesis and tumor progression of lymphoma is required. Epigenetic alterations contribute to cancer initiation, progression, and drug resistance. In fact, over the past decade, dysregulation of epigenetic mechanisms has been identified in lymphomas, and the knowledge of the epigenetic aberrations has led to the emergence of the promising epigenetic therapy field in lymphoma tumors. However, epigenetic aberrations in lymphoma not only have been found in tumor cells, but also in cells from the tumor microenvironment, such as immune cells. Whereas the epigenetic dysregulation in lymphoma cells is being intensively investigated, there are limited studies regarding the epigenetic mechanisms that affect the functions of immune cells from the tumor microenvironment in lymphoma. Therefore, this review tries to provide a general overview of epigenetic alterations that affect both lymphoma cells and infiltrating immune cells within the tumor, as well as the epigenetic cross-talk between them.