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非 HCV/非 HBV 肝细胞癌患者循环和肿瘤浸润免疫细胞的高度差异计数。

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

机构信息

Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377, Munich, Germany.

German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.

出版信息

Cancer Immunol Immunother. 2022 May;71(5):1103-1113. doi: 10.1007/s00262-021-03061-9. Epub 2021 Sep 28.

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.

摘要

背景

肝移植和肝切除术是早期肝细胞癌 (HCC) 的治愈方法。其结果部分取决于对恶性肿瘤的免疫反应。在这项研究中,我们旨在确定非 HCV/非 HBV HCC 患者的免疫特征。

方法

使用多色流式细胞术测量了 39 种免疫细胞亚群。对 10 例 HCC 切除患者和 10 名健康供体的外周血 (PB) 和肿瘤标本进行了这种免疫表型分析。使用多维技术分析高度差异白细胞计数 (hDIF) 的特征。使用细胞内 IFN-γ 染色测量功能能力(试验注册 DRKS00013567)。

结果

hDIF 显示出抗肿瘤反应的激活(T、B、NK 和树突状细胞亚群)和抑制(髓样来源的抑制细胞以及 T 和 B 调节细胞亚群)。PB 和肿瘤浸润性白细胞 (TIL) 的主成分分析说明了抗肿瘤激活梯度。TIL 通过分泌 IFN-γ 显示出功能能力,但不能杀死 HCC 细胞。

结论

总之,hDIF 的测量显示了针对非 HCV/非 HBV HCC 的免疫反应的明显差异,并说明了外周血向免疫抑制梯度的方向。

试验注册

DRKS00013567。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aa5/10991204/65534ce86d68/262_2021_3061_Fig1_HTML.jpg

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