LAUSR

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous type of non-Hodgkin’s lymphoma varied from clinical, pathological, immunophenotypic, molecular and prognostic features. According to gene expression profiling, DLBCL can be distinguished to three subtypes, germinal center B-like (GCB), activated B-cell like (ABC) and primary mediastinal B-cell lymphoma (PMBL) subtypes, the latter two referred as non-GCB subtype. As a more practical method, classification of GCB and non-GCB subtype is mostly detected by immunohistochemistry study of CD10, BCL6, MUM1. Nowadays, growing studies have applied system biology techniques to determine multiomic heterogeneity and to accomplish molecular classification in DLBCL. The immunotherapy of cancer has also made significant progress in the past decade. Improved understanding of cancer immunology increases insights into the mechanism of tumor response to immune cells, elucidating the therapeutic role of immunity in cancer and fueling an expanding array of new therapeutic agents. Evaluation of the effectiveness of immunotherapy involves various immune cells within peripheral blood or tumor, including monocytes, lymphocytes, myeloid-derived suppressor cells (MDSC), as well as inflammatory factors and cytokines, etc. In DLBCL, lymphocyte-monocyte ratio (LMR) and cytokines like sIL-2R, IL-6, IL-8, IL-10, and TNF-a are significantly associated with clinical outcome. From 1114 patients with nonHodgkin’s lymphoma, we develop a nomogram for OS prediction, including lactate dehydrogenase (LDH), LMR, sIL-2R, and TNF-a. Moreover, MDSC is a group of immune cells from the myeloid lineage, including granulocyte-like (G-MDSC) and monocytic (M-MDSC). MDSC has negative correlation with T cells and increased M-MDSC is related to poor disease outcome in DLBCL. Addition of immunoregulatory agents to R-CHOP proves efficient in treating high-risk DLBCL patients. Lenalidomide, an oral immunomodulatory agent, has shown activity in DLBCL. A phase III randomized study revealed that lenalidomide maintenance for 24 months after obtaining a CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL. Atezolizumab is a humanized anti-programmed death-ligand 1 (PD-L1) antibody. Another phase I/II open-label study enrolled advanced DLBCL patients. Among 40 evaluable patients for response, 31 patients (77.5%) had a CR and 4 patients (10%) had a PR. Together, immune dysregulation plays an important role on disease progression and may become potential therapeutic targets. Further mechanism study is helpful for the identification of biological subsets sensitive to immunotherapy and eventually to realize precision treatment in DLBCL.