Dataset Information

Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

ABSTRACT: Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.

SUBMITTER: Sun YF

PROVIDER: S-EPMC8253833 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

Sun Yun-Fan YF Wu Liang L Liu Shi-Ping SP Jiang Miao-Miao MM Hu Bo B Zhou Kai-Qian KQ Guo Wei W Xu Yang Y Zhong Yu Y Zhou Xiao-Rui XR Zhang Ze-Fan ZF Liu Geng G Liu Sheng S Shi Ying-Hong YH Ji Yuan Y Du Min M Li Nan-Nan NN Li Gui-Bo GB Zhao Zhi-Kun ZK Huang Xiao-Yun XY Xu Li-Qin LQ Yu Qi-Chao QC Peng David H DH Qiu Shuang-Jian SJ Sun Hui-Chuan HC Dean Michael M Wang Xiang-Dong XD Chung Wen-Yuan WY Dennison Ashley R AR Zhou Jian J Hou Yong Y Fan Jia J Yang Xin-Rong XR

Nature communications 20210702 1

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress ...[more]

PMID: 34215748

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Project description:Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the third leading cause of tumor-related mortality worldwide. In recent years, the emergency of immune checkpoint inhibitor (ICI) has revolutionized the management of HCC. Especially, the combination of atezolizumab (anti-PD1) and bevacizumab (anti-VEGF) has been approved by the FDA as the first-line treatment for advanced HCC. Despite great breakthrough in systemic therapy, HCC continues to portend a poor prognosis owing to drug resistance and frequent recurrence. The tumor microenvironment (TME) of HCC is a complex and structured mixture characterized by abnormal angiogenesis, chronic inflammation, and dysregulated extracellular matrix (ECM) remodeling, collectively contributing to the immunosuppressive milieu that in turn prompts HCC proliferation, invasion, and metastasis. The tumor microenvironment coexists and interacts with various immune cells to maintain the development of HCC. It is widely accepted that a dysfunctional tumor-immune ecosystem can lead to the failure of immune surveillance. The immunosuppressive TME is an external cause for immune evasion in HCC consisting of 1) immunosuppressive cells; 2) co-inhibitory signals; 3) soluble cytokines and signaling cascades; 4) metabolically hostile tumor microenvironment; 5) the gut microbiota that affects the immune microenvironment. Importantly, the effectiveness of immunotherapy largely depends on the tumor immune microenvironment (TIME). Also, the gut microbiota and metabolism profoundly affect the immune microenvironment. Understanding how TME affects HCC development and progression will contribute to better preventing HCC-specific immune evasion and overcoming resistance to already developed therapies. In this review, we mainly introduce immune evasion of HCC underlying the role of immune microenvironment, describe the dynamic interaction of immune microenvironment with dysfunctional metabolism and the gut microbiome, and propose therapeutic strategies to manipulate the TME in favor of more effective immunotherapy.

Dataset Information

Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

Publications

Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

Similar Datasets

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