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12.10.2023 | Original Article

Distinctly altered lipid components in hepatocellular carcinoma relate to impaired T cell-dependent antitumor immunity

verfasst von: Xue Cheng, Wei Wang, Ziyao Zhang, Haoquan Zhang, Peng Zhu, Ran He, Mi Wu, Ting Zhou, Ying Jiang, Lang Jiang, Yiqing Chen, Zhihui Liang, Xiongwen Wu, Xiufang Weng

Erschienen in: Hepatology International | Ausgabe 2/2024

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Abstract

Background and aims

T cells are master effectors of anti-tumor immunity in cancer. Recent studies suggest that altered lipid metabolism imposed by the tumor microenvironment constrains anti-tumor immunity. However, the tumor-associated lipid species changes that dampen T cell ability to control tumor progression are not fully understood. Here, we plan to clarify the influences of distinctly altered lipid components in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) on T-cell function, aiming to seek lipid metabolic targets for improving T cell anti-tumor effects.

Methods

Tumor tissues and non-tumor liver from HCC patients were collected for RNA-sequencing, lipid profiling and T cell characterizing, followed by correlation analysis. Additionally, the effects of significantly changed lipid components on anti-tumor potential of T cells were tested by in vitro cell experiments and/or in vivo tumor inoculated model.

Results

Altered lipid metabolism coincides with impaired T cell response in HBV-related HCC. Characteristic lipid composition, significantly marked by accumulation of long-chain acylcarnitines (LCACs) and reduction of lysophosphatidylcholines (LPCs), are found in the tumor tissue. Notably, LCACs accumulated are associated with T cells exhaustion and deficient functionality, while LPCs correlate to anti-tumor effects of T cells. In particular, supplement of LPCs, including LPC (20:0) and LPC (22:0), directly promote the activation and IFN-γ secretion of T cells in vitro, and suppress tumor growth in vivo.

Conclusions

Our study highlights the distinctly changed lipid components closely related to T cell dysregulation in HCC, and suggests a promising strategy by decreasing LCACs and increasing LPCs for anti-tumor immunotherapy.

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Titel: Distinctly altered lipid components in hepatocellular carcinoma relate to impaired T cell-dependent antitumor immunity
verfasst von: Xue Cheng
Wei Wang
Ziyao Zhang
Haoquan Zhang
Peng Zhu
Ran He
Mi Wu
Ting Zhou
Ying Jiang
Lang Jiang
Yiqing Chen
Zhihui Liang
Xiongwen Wu
Xiufang Weng
Publikationsdatum: 12.10.2023
Verlag: Springer India
Erschienen in: Hepatology International / Ausgabe 2/2024
Print ISSN: 1936-0533
Elektronische ISSN: 1936-0541
DOI: https://doi.org/10.1007/s12072-023-10595-w

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Abstract

Background and aims

Methods

Results

Conclusions

Graphical abstract

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