The immune microenvironment in malignant lymphoma

Abstract

Recent advances in immunotherapy have highlighted the importance of the tumor microenvironment. Lymphomas are a heterogeneous group of malignancies that arise from lymphocytes and typically develop in lymphoid tissues. It has been recognized that the elements of the lymphoma microenvironment are not mere bystanders to a host antitumor inflammatory response but are important components of the tumor that support proliferation, survival, and chemoresistance of lymphoma cells. Lymphoma cells have individual expression patterns of chemokine receptors and adhesion molecules, according to their histological subtypes, and the patterns of surface molecules determine the sites of tumor involvement. Lymphoma cells often depend on the signals provided by non-tumor cells, such as stromal cells and macrophages, through direct cell contact and paracrine factors. On the other hand, there are genetic and non-genetic mechanisms allowing lymphoma cells to escape from anti-tumor immunity, such as downregulation of HLA molecules, B2M, CD58, CD70, and/or upregulation of PD-L1 and PD-L2. Further understanding of the interactions of lymphoma cells and the tumor microenvironment gives an insight into the pathogenesis of lymphomas and supports new approaches to their treatment.