Epigenetic Symphony in Diffuse Large B-Cell Lymphoma: Orchestrating the Tumor Microenvironment

DLBCL is a testament to the complexity of nature. It is characterized by remarkable diversity in its molecular and pathological subtypes and clinical manifestations. Despite the strides made in DLBCL treatment and the introduction of innovative drugs, around one-third of patients face a relapse or develop refractory disease. Recent findings over the past ten years have highlighted the critical interplay between the evolution of DLBCL and various epigenetic mechanisms, including chromatin remodeling, DNA methylation, histone modifications, and the regulatory roles of non-coding RNAs. These epigenetic alterations are integral to the pathways of oncogenesis, tumor progression, and the development of therapeutic resistance. In the past decade, the identification of dysregulated epigenetic mechanisms in lymphomas has paved the way for an exciting field of epigenetic therapies. Crucially, these epigenetic transformations span beyond tumor cells to include the sophisticated network within the tumor microenvironment (TME). While the exploration of epigenetic dysregulation in lymphoma cells is thriving, the mechanisms affecting the functions of immune cells in the TME invite further investigation. This review is dedicated to weaving together the narrative of epigenetic alterations impacting both lymphoma cells with a focus on their infiltrating immune companions.