Targeting the Immune Microenvironment in Lymphomas of B-Cell Origin: From Biology to Clinical Application

Abstract

In lymphomas of B-cell origin, cancer cells orchestrate an inflammatory microenvironment of immune and stromal cells that sustain the tumor cell survival and growth, known as a tumor microenvironment (TME). The features of the TME differ between the different lymphoma types, ranging from extremely inflammatory, such as in Hodgkin lymphoma, to anergic, leading to immune deficiency and susceptibility to infections, such as in chronic lymphocytic leukemia. Understanding the characteristic features of the TME as well as the interactions between cancer and TME cells has given insight into the pathogenesis of most lymphomas and contributed to identify novel therapeutic targets. Here, we summarize the preclinical data that contributed to clarifying the role of the immune cells in the TME of different types of lymphomas of B-cell origin, and explain how the understanding of the biological background has led to new clinical applications. Moreover, we provide an overview of the clinical results of trials that assessed the safety and efficacy of drugs directly targeting TME immune cells in lymphoma patients.

Immune Landscape in Burkitt Lymphoma reveals M2-macrophage polarization and Correlation between PD-L1 expression and Non-Canonical EBV latency program

“…50, 51 52 Although PD-L1 expression has been largely investigated in B cell lymphomas, the distinction of its expression in cellular microenviroment and/or in tumour cells has not been made in most studies. [1][2][3][4] Here we showed that EBV in BL might induce PD-L1 expression on tumor cells in a minority of cases characterized by a non-canonical latency with LMP2A positivity. On the other hand, it might influence PD-L1 upregulation on TAMs also in cases with canonical EBV latency I.…”

“…Over recent years, the understanding of the biology of B-cell lymphomas has advanced significantly with the identification of the role played by the tumour microenvironment (TME) in lymphomagenesis. 1,2 The TME of B-cell lymphomas mainly contains variable numbers of mesenchymal stem cells, immune cells and soluble factors. The complex interplay between tumour cells and TME regulates tumorigenesis and provides novel targets for immunotherapies.…”

Immune Landscape in Burkitt Lymphoma Reveals M2-Macrophage Polarization and Correlation between PD-L1 Expression and Non-Canonical EBV Latency Program

“…Although PD-L1 expression has been largely investigated in B cell lymphomas, its expression in cellular microenviroment and in tumour cells has not been well defined in most studies [1][2][3][4] .…”

“…Over recent years, the understanding of the biology of B-cell lymphoma has advanced significantly with the identification of the role played by the tumour microenvironment (TME) in lymphomagenesis 1,2 . The TME of B-cell lymphomas mainly contains variable numbers of mesenchymal stem cells, immune cells and soluble factors.…”

Tumor-Associated Macrophages in Hematologic Malignancies: New Insights and Targeted Therapies

“…The TME of CHL is composed of mainly inflammatory immune cells and only a small percentage of the cells, approximately 1% are malignant Hodgkin Reed-Sternberg (HRS) cells [41]. Thus, the role played by macrophages is especially important in the pathogenesis of CHL.…”