Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma

Ho, Daniel Wai‐Hung; Tsui, Y; Chan, Lap Ki; Sze, Karen Man‐Fong; Zhang, Xin; Cheu, Jacinth Wing‐Sum; Chiu, Yung-Tuen; Lee, Joyce Man‐Fong; Chan, Albert Chi‐Yan; Cheung, E; Yau, Derek; Chia, Nam-Hung; Lo, Irene; Sham, Pak C.; Cheung, T.H.; Wong, Carmen Chak‐Lui; Ng, Irene Oi Lin

doi:10.1038/s41467-021-24010-1

Cited by 157 publications

(141 citation statements)

References 71 publications

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“…High and low risk subtypes of HPV may be considered a form of species heterogeneity, while integrations and deletions can be a source of mutational variation ( 123 , 137 ). Tumor heterogeneity based on viral and host gene expression (including single cell RNAseq), epigenetic modifications, and immune infiltration have been observed for cancers associated with HPV ( 138 ), MCPyV ( 139 ), HBV ( 140 ), HCV ( 141 ), and HTLV-1 ( 142 ), indicating that such heterogeneity is a general rule for viral and non-viral cancers. Variations in viral gene expression and genome copy number may also account for cancer-risk.…”

Section: Common Threads: Oncoviral Persistence and Plasticitymentioning

confidence: 99%

Oncogenic Viruses as Entropic Drivers of Cancer Evolution

Tempera

Lieberman

2021

Front.Virol.

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Viral infection is an indisputable causal factor for nearly 17% of all human cancers. However, the diversity and complexity of oncogenic mechanisms raises new questions as to the mechanistic role of viruses in cancer. Classical viral oncogenes have been identified for all tumor-associated viruses. These oncogenes can have multiple oncogenic activities that may or may not be utilized in a particular tumor cell. In addition, stochastic events, like viral mutation and integration, as well as heritable host susceptibilities and immune deficiencies are also implicated in tumorigenesis. A more contemporary view of tumor biology highlights the importance of evolutionary forces that select for phenotypes better adapted to a complex and changing environment. Given the challenges of prioritizing singular mechanistic causes, it may be necessary to integrate concepts from evolutionary theory and systems biology to better understand viral cancer-driving forces. Here, we propose that viral infection provides a biological “entropy” that increases genetic variation and phenotypic plasticity, accelerating the main driving forces of cancer cell evolution. Viruses can also influence the evolutionary selection criteria by altering the tumor microenvironment and immune signaling. Utilizing concepts from cancer cell evolution, population genetics, thermodynamics, and systems biology may provide new perspectives on viral oncogenesis and identify novel therapeutic strategies for treating viruses and cancer.

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Section: Common Threads: Oncoviral Persistence and Plasticitymentioning

confidence: 99%

Oncogenic Viruses as Entropic Drivers of Cancer Evolution

Tempera

Lieberman

2021

Front.Virol.

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“…Another scRNA-seq-based study has shown that M2 macrophages are the predominant population of TAMs in HCC. Ho et al have demonstrated that TAMs have high expression levels of two immunosuppressive molecules, i.e., leucocyte-associated immunoglobulin-like receptor 1 (LAIR1) and hepatitis A virus cellular receptor 2 (HAVCR2) (known as Tim-3) [17].…”

Section: Single-cell Approach To Defining Immune Profile In Hccmentioning

confidence: 99%

“…Recently, growing studies have characterized immune cell populations and identified intercellular cross-talk in the TME of HCC using single-cell RNA sequencing (scRNA-seq) technologies [17]. scRNA-seq are sophisticated technologies that have been effectively used in various research fields due to their ability to identify and analyze different cell types within tissues [18].…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy for Hepatocellular Carcinoma: New Prospects for the Cancer Therapy

Fasano

Baradaran

Brunetti

et al. 2021

Life

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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. HCC patients may benefit from liver transplantation, hepatic resection, radiofrequency ablation, transcatheter arterial chemoembolization, and targeted therapies. The increased infiltration of immunosuppressive immune cells and the elevated expression of immunosuppressive factors in the HCC microenvironment are the main culprits of the immunosuppressive nature of the HCC milieu. The immunosuppressive tumor microenvironment can substantially attenuate antitumoral immune responses and facilitate the immune evasion of tumoral cells. Immunotherapy is an innovative treatment method that has been promising in treating HCC. Immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT), and cell-based (primarily dendritic cells) and non-cell-based vaccines are the most common immunotherapeutic approaches for HCC treatment. However, these therapeutic approaches have not generally induced robust antitumoral responses in clinical settings. To answer to this, growing evidence has characterized immune cell populations and delineated intercellular cross-talk using single-cell RNA sequencing (scRNA-seq) technologies. This review aims to discuss the various types of tumor-infiltrating immune cells and highlight their roles in HCC development. Besides, we discuss the recent advances in immunotherapeutic approaches for treating HCC, e.g., ICIs, dendritic cell (DC)-based vaccines, non-cell-based vaccines, oncolytic viruses (OVs), and ACT. Finally, we discuss the potentiality of scRNA-seq to improve the response rate of HCC patients to immunotherapeutic approaches.

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“…In contrast, the formation of B cell dominant tertiary lymphoid structures was shown to reverse T cell exhaustion and lead to improved tumour responsiveness to immune checkpoint inhibitors [102,103]. Predictive and prognostic immune effector cell populations were also identified in scRNA-seq analyses of the breast [109], ovarian [111], lung [112,129], and liver cancers [130].…”

Section: Diversity Of the Tumour Immune Microenvironmentmentioning

confidence: 99%

High-Dimensional Single-Cell Transcriptomics in Melanoma and Cancer Immunotherapy

Quek

Bai

Long

et al. 2021

Genes

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Recent advances in single-cell transcriptomics have greatly improved knowledge of complex transcriptional programs, rapidly expanding our knowledge of cellular phenotypes and functions within the tumour microenvironment and immune system. Several new single-cell technologies have been developed over recent years that have enabled expanded understanding of the mechanistic cells and biological pathways targeted by immunotherapies such as immune checkpoint inhibitors, which are now routinely used in patient management with high-risk early-stage or advanced melanoma. These technologies have method-specific strengths, weaknesses and capabilities which need to be considered when utilising them to answer translational research questions. Here, we provide guidance for the implementation of single-cell transcriptomic analysis platforms by reviewing the currently available experimental and analysis workflows. We then highlight the use of these technologies to dissect the tumour microenvironment in the context of cancer patients treated with immunotherapy. The strategic use of single-cell analytics in clinical settings are discussed and potential future opportunities are explored with a focus on their use to rationalise the design of novel immunotherapeutic drug therapies that will ultimately lead to improved cancer patient outcomes.

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Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma

Cited by 157 publications

References 71 publications

Oncogenic Viruses as Entropic Drivers of Cancer Evolution

Oncogenic Viruses as Entropic Drivers of Cancer Evolution

Immunotherapy for Hepatocellular Carcinoma: New Prospects for the Cancer Therapy

High-Dimensional Single-Cell Transcriptomics in Melanoma and Cancer Immunotherapy

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