One Single Site Clinical Study: To Evaluate the Safety and Efficacy of Immunotherapy With Autologous Dendritic Cells, Cytokine-Induced Killer Cells in Primary Hepatocellular Carcinoma Patients.

Kaiyue Xu,Beicheng Sun,Yi Chai,Xiaoxin Mu,Zhengjie Meng

doi:10.3389/fonc.2020.581270

Abstract

Dendritic cells (DCs) and cytokine-induced killer (CIK) cells play an important role in the anti-tumor immune response. In this study, we evaluated the clinical effectiveness of DC/CIK-CD24 immunotherapies to primary hepatocellular carcinoma patients who received radical resection. 36 resected primary hepatocellular carcinoma (HCC) patients were enrolled from August 2014 to December 2015. All patients received two or four times of DC/CIK immunotherapy after radical resection. 1–4 years patients’ survival rates were evaluated during the follow-up. The 4-year survival rate of patients who received two times of immunotherapy was 47.1%, and the rate of those who received four times of immunotherapies was 52.6%. Compared to baseline, after receiving the DC/CIK-CD24 autotransfusion, the serum Treg concentration of the patients decreased, while CD3+, CD4+, CD56+ increased slightly. The adverse effect of immunotherapy was I–II° transient fever and could be tolerable. DC/CIK-CD24 immunotherapy can delay the relapse time.

Highlights

Primary liver cancer (PHC) is one of the most common malignant tumors in China, and approximately 80% of liver cancer are hepatocellular carcinoma (HCC) [1]
As the most effective antigen-presenting cells, Dendritic cells (DCs) have been applied as components of anti-tumor vaccines
DCs play an important role in anti-tumor immune response, such as capturing and presenting tumor-associated antigens and activating naive T cells, regulating T cell response, promoting cell synthesis, cytokine secretion [15]

Summary

INTRODUCTION

Primary liver cancer (PHC) is one of the most common malignant tumors in China, and approximately 80% of liver cancer are hepatocellular carcinoma (HCC) [1]. Immature DCs stimulated by tumor antigen is activated to induce synthesis of cells and secretion of cytokines including interleukin-2 (IL-2), Tumor necrosis factor-a (TNF-a), interferon-b (IFN-b) These cytokines are able to activate tumor-specific immune response by stimulating the initial T cells [8]. The combination of DCs and CIK cells, the main cell types used in immunotherapy, enhances the immune response and kills tumor cells through their cytotoxic activity [7, 11, 12]. Peripheral blood was collected from the patients on the 7th to 9th day after radical resection of the tumor. Data collected included vital signs, ECOG, laboratory examination (whole blood cell count, liver and kidney function test, coagulation index, tumor biomarkers, immune biomarkers), DC/CIK-CD24 autologous transfusion information, toxicity, and adverse events. P values less than 0.05 (two-tailed) were considered significant

RESULTS

DISCUSSION

ETHICS STATEMENT