Published online Mar 21, 2018. doi: 10.3748/wjg.v24.i11.1228
Peer-review started: November 6, 2017
First decision: November 27, 2017
Revised: December 24, 2017
Accepted: January 16, 2018
Article in press: January 16, 2018
Published online: March 21, 2018
Processing time: 130 Days and 19.8 Hours
To assess the levels of different immune modulators in patients with hepatocellular carcinoma (HCC), in relation to other hepatic diseases.
Eighty-eight patients were included in the current study and represented patients with HCC (20), liver cirrhosis (28) and chronic hepatitis (CH; 25), and normal controls (NC; 15). Peripheral blood was isolated for immunophenotyping of active myeloid dendritic cells (mDCs; CD1c and CD40), mature inactive myeloid cells (CD1c and HLA), active plasmacytoid cells (pDCs; CD303 and CD40), mature inactive pDCs (CD30 and HLA), active natural killer (NK) cells (CD56 and CD161), active NK cells (CD56 and CD314) and inactive NK cells (CD56 and CD158) was done by flow cytometry. Serum levels of interleukin (IL)-2, IL-10, IL-12, IL-1β, interferon (IFN)-α, IFN-γ and tumor necrosis factor (TNF)-αR2 were assessed by ELISA.
Active mDCs (CD1C+/CD40+) and inactive mDCs (CD1c+/HLA+) were significantly decreased in HCC patients in relation to NC (P < 0.001). CD40+ expression on active pDCs was decreased in HCC patients (P < 0.001), and its level was not significantly changed among other groups. Inactive pDCs (CD303+/HLA+), inactive NKs (CD56+/CD158+) and active NKs (CD56+/CD161+) were not statistically changed among the four groups studied; however, the latter was increased in CH (P < 0.05). NKG2D was statistically decreased in HCC, CH and cirrhosis (P < 0.001), and it was not expressed in 63% (12/20) of HCC patients. There was significant decrease of IL-2, IFN-α and IFN-γ (P < 0.001), and a significant increase in IL-10, IL-1β, and TNF-αR2 (P <0.01, P < 0.001 and P < 0.001; respectively) in HCC patients. There was inverted correlation between IL-12 and IL-1β in HCC (r = -0.565, P < 0.01), with a strong correlation between pDCs (CD303+/CD40+) and NKs (CD56+/CD161+; r = 0.512, P < 0.05) as well as inactive mDCs (CD1c+/HLA+) and inactive NK cells (CD56+/CD158+; r = 0.945, P < 0.001).
NKG2D, CD40, IL-2 and IL-10 are important modulators in the development and progression of HCC.
Core tip: We assessed the levels of different immune modulatory cytokines and innate immune cells as natural killer (NK) cells and dendritic cells (DCs) in patients with disease progression of hepatocarcinogenesis. Our results showed significant down-regulation in active mDCs and pDCs expressing CD40 as well as NK cells expressing NKG2D. The expression of NKG2D on NKs was not expressed in 63% of hepatocellular carcinoma (HCC) patients. Also, there was significant decrease of interleukin (IL)-2, interferon-α and interferon-γ, and a significant increase in IL-10, IL-1β, and TNF-αR2 in HCC patients. These factors could be implicated in the pathogenesis of HCC, and represent attractive targets for therapy in chronic hepatitis C virus hepatitis and HCC.