Microenvironment Cell Contribution to Lymphoma Immunity

Lymphoma microenvironment is a complex system composed of stromal cells, blood vessels, immune cells as well as extracellular matrix, cytokines, exosomes, and chemokines. In this review, we describe the function, localization, and interactions between various cellular components. We also summarize their contribution to lymphoma immunity in the era of immunotherapy. Publications were identified from searching Pubmed. Primary literature was carefully evaluated for replicability before incorporating into the review. We describe the roles of mesenchymal stem/stromal cells (MSCs), lymphoma-associated macrophages (LAMs), dendritic cells, cytotoxic T cells, PD-1 expressing CD4+ tumor infiltrating lymphocytes (TILs), T-cells expressing markers of exhaustion such as TIM-3 and LAG-3, regulatory T cells, and natural killer cells. While it is not in itself a cell, we also include a brief overview of the lymphoma exosome and how it contributes to anti-tumor effect as well as immune dysfunction. Understanding the cellular players that comprise the lymphoma microenvironment is critical to developing novel therapeutics that can help block the signals for immune escape and promote tumor surveillance. It may also be the key to understanding mechanisms of resistance to immune checkpoint blockade and immune-related adverse events due to certain types of immunotherapy.