Changes in immune profile affect disease progression in hepatocellular carcinoma

Farshid Fathi; Reza F Saidi; Hamid Reza Banafshe; Mohsen Arbabi; Majid Lotfinia; Hossein Motedayyen

doi:10.1177/03946320221078476

Changes in immune profile affect disease progression in hepatocellular carcinoma

Int J Immunopathol Pharmacol. 2022 Jan-Dec:36:3946320221078476. doi: 10.1177/03946320221078476.

Authors

Farshid Fathi¹, Reza F Saidi², Hamid Reza Banafshe³, Mohsen Arbabi⁴, Majid Lotfinia³, Hossein Motedayyen⁵

Affiliations

¹ Department of Immunology, School of Medicine, 48455Isfahan University of Medical Sciences, Isfahan, Iran.
² Division of Transplant Services, Department of Surgery, 12302SUNY Upstate Medical University Syracuse, Syracuse, NY, USA.
³ Physiology Research Center, 48462Kashan University of Medical Sciences, Kashan, Iran.
⁴ Department of Medical Parasitology, 48462Kashan University of Medical Sciences, Kashan, Iran.
⁵ Autoimmune Diseases Research Center, 48462Kashan University of Medical Sciences, Kashan, Iran.

Abstract

Objective: Hepatocellular carcinoma (HCC) as a chronic liver condition is largely associated with immune responses. Previous studies have revealed that different subsets of lymphocytes play fundamental roles in controlling or improving the development and outcome of solid tumors like HCC. Hence, this study aimed to investigate whether immune system changes were related to disease development in HCC patients. Methods: Peripheral blood mononuclear cells were isolated from 30 HCC patients and 30 healthy volunteers using Ficoll density centrifugation. The isolated cells were stained with different primary antibodies and percentages of different immune cells were determined by flow cytometry. Results: HCC patients indicated significant reductions in the numbers of CD4⁺ cells, Tbet+IFNγ+cells, and GATA+IL-4+cells in peripheral blood in comparison with healthy individuals (p < 0.05). There was no significant change in IL-17+RORγt+cells between patient and healthy groups. In contrast, Foxp3+CD127^lowcell frequency was significantly higher in patients than healthy subjects (p < 0.0001). The numbers of Th1, Th2, and Th17 cells were significantly lower in HCC patients than healthy control (p < 0.0001), although the reduction in Th2 cell numbers was not statistically significant. On the contrary, Treg percentage showed a significant increase in patients compared to healthy subjects (p < 0.0001). Other data revealed that Th1, Th2, and Th17 cell frequencies were significantly higher in healthy individuals than patients with different TNM stages of HCC, with the exception of Th2 in patients with stage II HCC (p < 0.01-0.05). Treg percentage was significantly increased in patients with different TNM stages (p < 0.0001). Among all CD4⁺ T cells, the frequency of Th2 cell was significantly associated with TNM stages of HCC (p < 0.05). Conclusion: Our data provide further evidence to show that immune changes may participate in determining HCC progression and disease outcome. However, it should be mentioned that more investigations are needed to clarify our results and explain possible impacts of other immune cells on the pathogenesis of HCC.

Keywords: T helper cells; cellular immunity; hepatocellular carcinoma; immune system.

MeSH terms

Carcinoma, Hepatocellular*
Disease Progression
Humans
Leukocytes, Mononuclear
Liver Neoplasms*
T-Lymphocytes, Regulatory
Th1 Cells
Th17 Cells
Th2 Cells