Systematic characterization of the tumor microenvironment in Chinese patients with hepatocellular carcinoma highlights intratumoral B cells as a potential immunotherapy target

Surgical resection is the first-line curative treatment modality for resectable hepatocellular carcinoma (HCC). Anatomical resection (AR), described as systematic removal of a liver segment confined by tumor-bearing portal tributaries, may improve survival by reducing the risk of tumor recurrence compared with non-AR. In this article, we propose the rationale for AR and its universal adoption by providing supporting evidence from the advanced understanding of a tumor microenvironment and accumulating clinical experiences of locoregional tumor ablation therapeutics. AR may be advantageous because it completely removes the en-bloc by interrupting tumor vascular supply and thus extirpates the spreading of tumor microthrombi, if they ever exist, within the supplying portal vein. However, HCC is a hypervascular tumor that can promote neoangiogenesis in the local tumor microenvironment, which in itself can break through the anatomical boundary within the liver and even retrieve nourishment from extrahepatic vessels, such as inferior phrenic or omental arteries. Additionally, increasing clinical evidence for locoregional tumor ablation therapies, such as radiofrequency ablation, predominantly performed as a non-anatomical approach, suggests comparable outcomes for surgical resection, particularly in small HCC and colorectal, hepatic metastases. Moreover, liver transplantation for HCC, which can be considered as AR of the whole liver followed by implantation of a new graft, is not universally free from post-transplant tumor recurrence. Overall, AR should not be considered the gold standard among all surgical resection methods. Surgical resection is fundamentally reliant on choosing the optimal margin width to achieve en-bloc tumor niche removal while balancing between oncological radicality and the preservation of postoperative liver function. The importance of this is to liberate surgical resilience in hepatocellular carcinoma. The overall success of HCC treatment is determined by the clearance of the theoretical niche. Developing biomolecular-guided navigation device/technologies may provide surgical guidance toward the total removal of microscopic tumor niche to achieve superior oncological outcomes.

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Current Trends in Non-Invasive Imaging of Interactions in the Liver Tumor Microenvironment Mediated by Tumor Metabolism

Cancers ◽

10.3390/cancers13153645 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3645

Author(s):

Isabel Theresa Schobert ◽

Lynn Jeanette Savic

Keyword(s):

Tumor Microenvironment ◽

Liver Cancer ◽

Cancer Cells ◽

Imaging Techniques ◽

Treatment Strategies ◽

Tumor Metabolism ◽

Resistance Mechanisms ◽

Metabolic Reprogramming ◽

Non Invasive

With the increasing understanding of resistance mechanisms mediated by the metabolic reprogramming in cancer cells, there is a growing clinical interest in imaging technologies that allow for the non-invasive characterization of tumor metabolism and the interactions of cancer cells with the tumor microenvironment (TME) mediated through tumor metabolism. Specifically, tumor glycolysis and subsequent tissue acidosis in the realms of the Warburg effect may promote an immunosuppressive TME, causing a substantial barrier to the clinical efficacy of numerous immuno-oncologic treatments. Thus, imaging the varying individual compositions of the TME may provide a more accurate characterization of the individual tumor. This approach can help to identify the most suitable therapy for each individual patient and design new targeted treatment strategies that disable resistance mechanisms in liver cancer. This review article focuses on non-invasive positron-emission tomography (PET)- and MR-based imaging techniques that aim to visualize the crosstalk between tumor cells and their microenvironment in liver cancer mediated by tumor metabolism.

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Metabolic reprogramming of immune cells: Shaping the tumor microenvironment in hepatocellular carcinoma

Cancer Medicine ◽

10.1002/cam4.4177 ◽

2021 ◽

Author(s):

Yujia Xia ◽

Zachary J. Brown ◽

Hai Huang ◽

Allan Tsung

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Microenvironment ◽

Immune Cells ◽

Metabolic Reprogramming

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New Insights into the Role of miR-29a in Hepatocellular Carcinoma: Implications in Mechanisms and Theragnostics

Journal of Personalized Medicine ◽

10.3390/jpm11030219 ◽

2021 ◽

Vol 11 (3) ◽

pp. 219

Author(s):

Ya-Ling Yang ◽

Yen-Hsiang Chang ◽

Chia-Jung Li ◽

Ying-Hsien Huang ◽

Ming-Chao Tsai ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Microenvironment ◽

Crucial Role ◽

Human Cancer ◽

Metabolic Adaptation ◽

Advanced Hcc ◽

Diagnosis And Prognosis ◽

Competitive Endogenous Rnas ◽

Growing Body

Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of tumor microenvironment (TME) is complex and inconclusive. A growing body of studies demonstrate microRNAs (miRs) are important regulators in the tumorigenicity and TME development. Notably, mounting evidences indicate miR-29a play a crucial role in exerting hepatoprotective effect on various types of stress and involved in the progression of HCC, which elucidates their potential theragnostic implications. In this review, we reviewed the advanced insights into the detail mechanisms by which miR-29a dictates carcinogenesis, epigenetic program, and metabolic adaptation, and implicated in the sponging activity of competitive endogenous RNAs (ceRNA) and the TME components in the scenario of HCC. Furthermore, we highlighted its clinical significance in diagnosis and prognosis, as well as the emerging therapeutics centered on the activation of miR-29a.

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