Abstract
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.
Highlights
Lymphomas are a diverse group of clonal neoplasms arising from B and T lymphocytes, and natural killer (NK) cells and are characterized by infiltration of lymphoid structures.Most of these neoplasms correspond to the normal stages of B-cell or T-cell differentiation and can be classified [1]
The primary goal of this review is to address the interplay between lymphoma cells and the cells of the lymphoma microenvironment and to understand how this communication leads to mechanisms of immune evasion and tumor proliferation
The lymphoma microenvironment is a complex stage where the actors can interact with each other in varying ways depending on the context
Summary
The cellular context in which lymphoma cells thrive has only recently become an important focus of inquiry. Our understanding of cytogenetic abnormalities and molecular pathways in lymphoma are in advance of solid organ tumors, the same cannot be said of the tumor microenvironment. We summarize some of the major components of the lymphoma microenvironment and their contribution to lymphoma immunity. The primary goal of this review is to address the interplay between lymphoma cells and the cells of the lymphoma microenvironment and to understand how this communication leads to mechanisms of immune evasion and tumor proliferation. Our manuscript will present some of the controversies in the field and present the limitations in our understanding of the roles and responsibilities of the microenvironment cell in lymphoma pathogenesis
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