Elevated M-MDSCs in Circulation Are Indicative of Poor Prognosis in Diffuse Large B-Cell Lymphoma Patients

Abstract

Myeloid-derived suppressor cells (MDSCs) are defined as negative regulators that suppress the immune response through a variety of mechanisms, which usually cluster in cancer, inflammation, and autoimmune diseases. This study aims to investigate the correlation between M-MDSCs and the clinical features of diffuse large B-cell lymphoma (DLBCL) patients, as well as the possible accumulation mechanism of M-MDSCs. The level of M-MDSCs is significantly increased in newly diagnosed and relapsed DLBCL patients. Regarding newly diagnosed DLBCL patients, the frequency of M-MDSCs is positively correlated with tumor progression and negatively correlated with overall survival (OS). More importantly, the level of M-MDSCs can be defined as a biomarker for a poor prognosis in DLBCL patients. Additionally, interleukin-35 (IL-35) mediates the accumulation of M-MDSCs in DLBCL patients. Anti-IL-35 treatment significantly reduces levels of M-MDSCs in Ly8 tumor-bearing mice. Thus, M-MDSCs are involved in the pathological process of DLBCL. Targeting M-MDSCs may be a promising therapeutic strategy for the treatment of DLBCL patients.

Decoding the Myeloid-Derived Suppressor Cells in Lymphoid Malignancies

“…Based on the median value frequency of M-MDSCs (25.4%), DLBCL patients were divided into two groups: low (n = 39) with M-MDSCs levels ≤ 25.4% and the high group (n = 26) with M-MDSCs levels > 25.4%. The OS of DLBCL patients with low M-MDSC levels was significantly longer than those with high M-MDSC levels (p < 0.01) [94]. In multivariate analysis, IPI and MDSCs levels were independent prognostic factors for OS.…”

“…At day 23, after tumor induction, they sacrificed them, collected blood, and analyzed their M-MDSC populations. Importantly, they found that tumor-bearing mice treated with neutralizing anti-IL35 antibodies had a reduced accumulation of M-MDSCs, indicating that anti-IL-35 treatment blocked M-MDSC expansion, creating expectations for their possible future use as a new therapeutic strategy for DLBCL patients [94].…”

“…Analyses of PMN-MDSCs were also excluded from a recent study by Wang et al, in which 103 DLBCL patients (65 newly diagnosed, 12 in relapse, and 26 in remission) and 30 healthy controls were examined for M-MDSCs' (CD14 + HLADR −/low ) frequencies in their peripheral blood [94]. Notably, a significantly increased frequency of M-MDSCs was found in the 65 newly diagnosed as well as relapsed DLBCL patients compared to patients in remission and healthy controls.…”

Suppressing MDSC Recruitment to the Tumor Microenvironment by Antagonizing CXCR2 to Enhance the Efficacy of Immunotherapy

“…Tumor cell-extrinsic mechanisms of immunotherapy resistance include low infiltration of tumor antigen-specific T cells and the presence of immunosuppressive cells such as MDSCs and tumor-associated macrophages (TAMs) [ 6 ]. Elevated numbers of MDSCs are associated with poor response to therapy, including, immunotherapy across several tumor types [ 7 , 8 , 9 ]. High numbers of MDSCs in the peripheral blood were associated with poor overall survival in a phase I/II study of melanoma patients treated with anti-PD1 therapy after progressing on anti-CTLA4 therapy [ 10 ].…”

Myeloid-Derived Suppressor Cells (MDSCs) in Haematology

“…Not only have they found that M-MDSCs are increased in the PB of the patients, but these cells are also correlated with poor prognosis, as the authors presented a positive correlation of M-MDSCs with the international prognostic index (IPI) score and a negative correlation with the overall survival in their patients. Through further in vitro and in vivo experiments, the authors suggested a possible mechanism of the accumulation of these cells in DLBCL, and this is via interleukin-35 (IL-35), which is known to be increased in this condition [ 6 ].…”