Clinical and prognostic significance of CD14 (+) HLA‐DR (−/low) myeloid‐derived suppressor cells in patients with hepatocellular carcinoma received transarterial radioembolization with Yttrium‐90

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. For unresectable HCC, transarterial radioembolization (TARE) with Yttrium‐90 is a widely used treatment. The aim of this study was to investigate whether monocytic myeloid‐derived suppressor cells (M‐MDSC) and CD39+ T cells can be non‐invasive predictive biomarkers of radiological response and prognosis in patients with HCC treated with TARE. This study was conducted on 39 patients with HCC who were treated with TARE between August 2018 and December 2019 and the control group consisted of 23 healthy volunteers. CD4+, CD8+, CD39+ T cells, Natural killer (NK) cells, myeloid cells (MC) and M‐MDSC parameters are examined in the course of TARE treatment with student t test and Kaplan‐Meier method. There were statistically significant differences in M‐MDSC, CD39+ T cells and MC values between healthy controls and HCC patients. A statistically significant difference was found in M‐MDSC and CD4+ T cells values in the HCC patient group who responded to the treatment compared to those who did not. Survival analysis found that patients with lower frequencies (under 3.81%) of M‐MDSC showed more prominent differences of overall survival (OS) compared to patients with all high groups. We found that M‐MDSC in the peripheral blood might be a useful non‐invasive biomarker to predict OS. We have shown for the first time that M‐MDSC is correlated with treatment response in HCC patients treated with TARE. Additionally, we have found that the percentage of CD39+ T cells is high in HCC patients and these cells are positively correlated with M‐MDSC.

Myeloid-Derived Suppressor Cells: Therapeutic Target for Gastrointestinal Cancers

“…MDSC infiltration is also associated with recurrence after local therapies in hepatocellular carcinoma. For example, the frequency of MDSCs after hepatic artery infusion therapy, yttrium-90 TARE, or radiotherapy is inversely linked with prognosis [ 24 , 25 , 26 ]. Following surgery, cytokine alpha interferon (IFNa) secretion drives recruitment of M-MDSCs, suppressing the activity of CD8-T-cells to drive recurrence [ 27 ].…”

Monocytes in Tumorigenesis and Tumor Immunotherapy

“…In acute myeloid leukemia (AML), elevated M-MDSC count is significantly associated with poor prognosis [ 64 ]. Circulating CD14 + HLA-DR lo/− monocytic MDSCs as an immune suppressive subset have potential clinical relevance for epithelial ovarian cancer progression [ 50 ] and HCC patients treated with trans-arterial radioembolization [ 65 ]. M-MDSCs are negatively associated with therapeutic response to immunotherapy, particularly CAR-T therapy [ 66 , 67 , 68 , 69 ], and with chemotherapy resistance [ 66 , 70 ].…”

Tumor Microenvironment CD14+ Cells Correlate with Poor Overall Survival in Patients with Early-Stage Lung Adenocarcinoma

“…This in vitro model of the cancer TME generates CD14 + HLA-DR lo/neg cells with decreased capacity to mature into dendritic cells, elaborate proangiogenic factors, and potently inhibit T-cell proliferation, similar to what is observed with cancer-patient-derived CD14 + HLA-DR lo/neg cells [ 11 , 12 , 13 ]. Clinically, an increasing burden of peripheral-blood-circulating CD14 + HLA-DR lo/neg cells correlates with poor patient outcomes across multiple tumor types, including NSCLC [ 10 , 11 , 14 , 15 , 16 , 17 , 18 , 19 ]. Recently, the higher levels of TME CD14 + cells were found to be associated with reduced survival in early-stage squamous NSCLC [ 20 ].…”