Highly differential count of circulating and tumor infiltrating immune cells in patients with non-HCV/non-HBV hepatocellular carcinoma

Abstract

Background Liver transplantation and liver resection are curative options for early hepatocellular carcinoma (HCC). The outcome is in part depended on the immunological response to the malignancy. In this study, we aimed to identify immunological profiles of non-HCV/non-HBV HCC patients. Methods Thirty-nine immune cell subsets were measured with multicolor flow cytometry. This immunophenotyping was performed in peripheral blood (PB) and tumor specimens of 10 HCC resection patients and 10 healthy donors. The signatures of the highly differential leukocyte count (hDIF) were analyzed using multidimensional techniques. Functional capability was measured using intracellular IFN-γ staining (Trial Registration DRKS00013567). Results The hDIF showed activation (subsets of T-, B-, NK- and dendritic cells) and suppression (subsets of myeloid-derived suppressor cells and T- and B-regulatory cells) of the antitumor response. Principal component analysis of PB and tumor infiltrating leukocytes (TIL) illustrated an antitumor activating gradient. TILs showed functional capability by secreting IFN-γ but did not kill HCC cells. Conclusions In conclusion, the measurement of the hDIF shows distinct differences in immune reactions against non-HBV/non-HCV HCC and illustrates an immunosuppressive gradient toward peripheral blood. Trial Registration DRKS00013567

Dynamics of Peripheral Blood Immune Cells during the Perioperative Period after Digestive System Resections: A Systematic Analysis of the Literature

“…The opposite results obtained by Shi et al were interpreted by the authors as an effect of removing the tumor lesion, which might have had an immunosuppressive effect. Both effects might be present and differently pronounced dependent on tumor type, size, and differentiation, or for example, liver cirrhosis, which also can lead to immunosuppression [ 41 , 42 ].…”

“…The effect of hepatitis or general chronic inflammation cannot be underestimated. Therefore, in our experimental work we have opted to investigate non-HBV/non-HCV patients to mitigate these biases [ 42 ]. Lastly, the invasiveness of the operation seems to be influencing the amount of immunosuppression deriving from the trauma.…”

Tertiary Lymphatic Structures in Primary Hepatic Carcinoma: Controversy Cannot Overshadow Hope

“…In addition, inhibitory TME has an important influence on tumor immunity. Some scholars have found that in non-HBV/non-HCV HCC, although TILs secrete IFN-γ, they cannot kill cancer cells ( 143 ). Therefore, the conversion of inhibitory TME into immunoactive TME is a key focus for HCC treatment.…”

CRISPR/Cas9 for hepatitis B virus infection treatment

“…The problems caused by chronic hepatitis B virus (HBV) infection continue to pose a major challenge to global health. 1 , 2 , 3 Although an effective preventive vaccine is available, it is of little use to people chronically infected with HBV. In addition, the existing treatment methods have limited efficacy and can not reliably eliminate all replication intermediates of the virus.…”

“…The problems caused by chronic hepatitis B virus (HBV) infection continue to pose a major challenge to global health 1–3 . Although an effective preventive vaccine is available, it is of little use to people chronically infected with HBV.…”