Hepatocellular carcinoma organoid co-cultures mimic angiocrine crosstalk to generate inflammatory tumor microenvironment

Lim, Joanne Tze Chin; Kwang, Leng Gek; Ho, Nicholas Ching Wei; Toh, Clarissa Chin Min; Too, Nathaniel Sheng Hua; Hooi, Lissa; Benoukraf, Touati; Chow, Pierce Kah‐Hoe; Dan, Yock Young; Chow, Edward Kai‐Hua; Toh, Tan Boon; Fong, Eliza Li Shan

doi:10.1016/j.biomaterials.2022.121527

Cited by 38 publications

(32 citation statements)

References 46 publications

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“…In addition, co-culture of cells of a specific type within TME with tumor organoids can also help partially characterize TME. This has been successful in some tumor organoids (53,55,56).…”

Section: The Disadvantage and Perspective Of Hcc Organoids For Target...mentioning

confidence: 99%

Opportunities and challenges of hepatocellular carcinoma organoids for targeted drugs sensitivity screening

Xie

Khan

et al. 2023

Front. Oncol.

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Hepatocellular carcinoma is one of the malignancies worldwide with a high mortality rate and an increasing incidence. Molecular Targeted agents are its common first-line treatment. Organoid technology, as a cutting-edge technology, is gradually being applied in the development of therapeutic oncology. Organoid models can be used to perform sensitivity screening of targeted drugs to facilitate the development of innovative therapeutic agents for the treatment of hepatocellular carcinoma. The purpose of this review is to provide an overview of the opportunities and challenges of hepatocellular carcinoma organoids in targeted drug sensitivity testing as well as a future outlook.

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“…In addition, co-culture of cells of a specific type within TME with tumor organoids can also help partially characterize TME. This has been successful in some tumor organoids (53,55,56).…”

Section: The Disadvantage and Perspective Of Hcc Organoids For Target...mentioning

confidence: 99%

Opportunities and challenges of hepatocellular carcinoma organoids for targeted drugs sensitivity screening

Xie

Khan

et al. 2023

Front. Oncol.

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“…Further, MCTS models comprising cancer cells and HUVEC or other endothelial cells can better reveal possible antiangiogenic activity, which increases metastasis compared to in vitro monolayer cultures. It was shown that 3D co-cultures of patient-derived xenograft organoids or HCC cells with endothelial cells increase the expression of CXCL16, IL-8, and MCP-1, indicating effective HCC cell-endothelial cells interactions in the 3D model (36). Interactions in the in vitro coculture of peripheral blood mononuclear cells (PBMCs) with HCC cells and non-HCC hepatocytes increase antigen presentation by HCC hepatocytes and activate PBMCs, leading to apoptosis of activated CD8+ T cells.…”

Section: Challenges In Using Model Systems To Recapitulate Liver Diseasementioning

confidence: 99%

Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models

Kim

Lee

Seo

2023

BMB Rep

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Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal.Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo.However, the information provided by an MCTS model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases. clinical utility of drugs that proved effective in vitro is low. Also, assays of liver function, including cell polarization, albumin synthesis, bile secretion, and urea synthesis, are better when they are performed in three-dimensional (3D) cell cultures that more accurately reflect the normal context of liver cells (7). Similarly, 3D cells provide a better model system for cancer drug discovery.The interactions between the tumor and the tumor microenvironment (TME) play a critical role in cell differentiation, tumorigenesis, metastasis, and the efficacy of drug therapies. Therefore it was important to develop a 3D TME platform to discover new therapeutics for liver cancer drug discovery. These platforms are complex and expensive to produce; however, the recently developed multicellular tumor spheroid (MCTS) models provide a new platform for highthroughput screening (HTS) of drugs to treat a variety of diseases, including cancers and infections.The development of 3D multicellular hepatic spheroid (MCHS) models has had a major impact on drug discovery and the identification of novel targets for the treatment of HCC and fibrosis. MCHS models should greatly increase the number of potential new drugs to treat HCC and reduce the time to drug discovery.In this review, we describe the influence of components of the TME on tumorigenesis, fibrogenesis, and chemoresistance in HCC, as well as advanced strategies that exploit 3D multicellular spheroid models to identify novel cancer targets and therapeutics.

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“…While tumour organoids have offered insight into how TAMs may act as friend or foe, caution must be taken when optimising the culture conditions (especially the external growth factor/cytokine supply), as they might shift the phenotypes of many cell types and mask the true effect of tumour–immune interaction. Future organoid-based TAM research may detail how TAMs cause T cell dysfunction [ 99 ], tumour cell inflammation, metabolic derangements [ 100 ], and increased angiogenesis [ 101 , 102 ] (discussed below). In fact, an M1–M2 dichotomy may be an oversimplification for TAMs in vivo, which can possess markers for both M1 and M2 at the same time [ 103 ].…”

Section: Translational Immuno-oncology Research With Organoidsmentioning

confidence: 99%

Organoids as an Enabler of Precision Immuno-Oncology

Zhao

Fong

Seow

et al. 2023

Cells

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Since the dawn of the past century, landmark discoveries in cell-mediated immunity have led to a greater understanding of the innate and adaptive immune systems and revolutionised the treatment of countless diseases, including cancer. Today, precision immuno-oncology (I/O) involves not only targeting immune checkpoints that inhibit T-cell immunity but also harnessing immune cell therapies. The limited efficacy in some cancers results mainly from a complex tumour microenvironment (TME) that, in addition to adaptive immune cells, comprises innate myeloid and lymphoid cells, cancer-associated fibroblasts, and the tumour vasculature that contribute towards immune evasion. As the complexity of TME has called for more sophisticated human-based tumour models, organoids have allowed the dynamic study of spatiotemporal interactions between tumour cells and individual TME cell types. Here, we discuss how organoids can study the TME across cancers and how these features may improve precision I/O. We outline the approaches to preserve or recapitulate the TME in tumour organoids and discuss their potential, advantages, and limitations. We will discuss future directions of organoid research in understanding cancer immunology in-depth and identifying novel I/O targets and treatment strategies.

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Hepatocellular carcinoma organoid co-cultures mimic angiocrine crosstalk to generate inflammatory tumor microenvironment

Cited by 38 publications

References 46 publications

Opportunities and challenges of hepatocellular carcinoma organoids for targeted drugs sensitivity screening

Opportunities and challenges of hepatocellular carcinoma organoids for targeted drugs sensitivity screening

Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models

Organoids as an Enabler of Precision Immuno-Oncology

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