Current perspectives on the tumor microenvironment in hepatocellular carcinoma

Santhakumar, Cositha; Gane, Edward; Liu, Ken; McCaughan, Geoffrey W.

doi:10.1007/s12072-020-10104-3

Cited by 57 publications

(54 citation statements)

References 106 publications

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“…In HCC, TME is immunosuppressive, thereby inducing tolerance and promotes the proliferation, invasion, and metastasis of tumors. The mentioned tumorigenic response is mediated from environmental cues, carcinogenic processes, several immunosuppressive cell subsets, inflammation-related molecules and signaling channels (5)(6)(7). Immunotherapy is gradually emerging in tumor treatment, especially immune checkpoint inhibitors (ICIs), which have suggested an encouraging efficacy that has changed the treatment model of advanced HCC.…”

Section: Introductionmentioning

confidence: 99%

Current Perspectives on B Lymphocytes in the Immunobiology of Hepatocellular Carcinoma

et al. 2021

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Immune cells infiltrating tumors are capable of significantly impacting carcinogenesis through cancer promotion and anticancer responses. There are many aspects of hepatocellular carcinoma (HCC) related T lymphocytes that are undergoing extensive studies, whereas the effect exerted by B lymphocytes remains a less researched area. In this study, the latest research on the effect of B lymphocytes as they infiltrate tumors in relation to HCC is presented. Their prognosis-related importance is analyzed, along with their function in the tumor microenvironment (TME), as well as the way that B cell biology can be employed to help create a B cell therapy strategy for HCC.

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Section: Introductionmentioning

confidence: 99%

Current Perspectives on B Lymphocytes in the Immunobiology of Hepatocellular Carcinoma

et al. 2021

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“…Many of the patients suffering from HCC were diagnosed at intermediate and advanced stages of tumor; however, the effective treatments for these patients are limited because of its complex pathogenesis ( Dhanasekaran et al, 2016 ). Of note, emerging evidence has defined the crucial role of the tumor microenvironment (TME) in the development and progression of HCC ( Santhakumar et al, 2020 ). The cellular and non-cellular components of the tumor niche supporting the tumor growth and metastasis comprise TME, where dynamic interactions between cancer cells and immune cells significantly impact tumor growth and therapy efficacy ( Wang et al, 2017 ; Arora and Pal, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression

Davuluri

Chen

Chiu

et al. 2021

Front. Cell Dev. Biol.

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Galectin-1 (Gal-1) is a secretory lectin with pro-tumor activities and is associated strongly with hepatocellular carcinoma (HCC) development. Although Gal-1 is a well-known soluble pro-tumor factor in the tumor microenvironment (TME), the secretion mode of Gal-1 is not clearly defined. On the other hand, in addition to cancer cells, Gal-1 is widely expressed in tumor stromal cells, including tumor-associated macrophages (TAMs). TAMs are a significant component of stromal cells in TME; however, their contributions in producing Gal-1 to TME are still not explored. Here we reveal that TAMs can actively secrete Gal-1 in response to stimuli of HCC cells. Gal-1 produced by TAMs leads to an increase of the systemic level of Gal-1 and HCC tumor growth in mice. Mechanistically, TLR2-dependent secretory autophagy is found to be responsible for Gal-1 secretion from TAMs. Gal-1 acts as a cargo of autophagosomes to fuse with multivesicular bodies via Rab11 and VAMP7-mediated vesicle trafficking before being secreted. This autophagy-regulated Gal-1 secretion in TAMs correlates to poor overall survival and progression-free survival rates of HCC patients. Our findings uncover the secretion mode of Gal-1 via secretory autophagy and highlight the pathological role of TAM-produced Gal-1 in HCC progression.

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“…Epigenetics is the heritable modification of gene function without changes in the DNA sequence, which is mediated by a number of different factors, including but not limited to, DNA methylation, histone modifications, and non-coding RNAs (22,23). Epigenetic regulation in tumor cells is extensively studied and plays critical roles in HCC development (24)(25)(26). Emerging evidence demonstrates that epigenetic alterations in TME also contribute to the initiation and progression of HCC (27)(28)(29)(30)(31)(32)(33).…”

Section: Introductionmentioning

confidence: 99%

The Epigenetic Regulation of Microenvironment in Hepatocellular Carcinoma

2021

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Hepatocellular carcinoma (HCC) is a highly lethal and complex malignancy strongly influenced by the surrounding tumor microenvironment. The HCC microenvironment comprises hepatic stellate cells (HSCs), tumor-associated macrophages (TAMs), stromal and endothelial cells, and the underlying extracellular matrix (ECM). Emerging evidence demonstrates that epigenetic regulation plays a crucial role in altering numerous components of the HCC tumor microenvironment. In this review, we summarize the current understanding of the mechanisms of epigenetic regulation of the microenvironment in HCC. We review recent studies demonstrating how specific epigenetic mechanisms (DNA methylation, histone regulation, and non-coding RNAs mediated regulation) in HSCs, TAMs, and ECM, and how they contribute to HCC development, so as to gain new insights into the treatment of HCC via regulating epigenetic regulation in the tumor microenvironment.

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Current perspectives on the tumor microenvironment in hepatocellular carcinoma

Cited by 57 publications

References 106 publications

Current Perspectives on B Lymphocytes in the Immunobiology of Hepatocellular Carcinoma

Current Perspectives on B Lymphocytes in the Immunobiology of Hepatocellular Carcinoma

Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression

The Epigenetic Regulation of Microenvironment in Hepatocellular Carcinoma

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