Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options

Zuzanna Sas, Ewa Cendrowicz, Isabel Weinhauser, Tomasz P. Rygiel*

*Corresponding author for this work

    Research output: Contribution to journalReview articleAcademicpeer-review

    2 Citations (Scopus)
    5 Downloads (Pure)

    Abstract

    The prevalence of liver cancer is constantly rising, with increasing incidence and mortality in Europe and the USA in recent decades. Among the different subtypes of liver cancers, hepatocellular carcinoma (HCC) is the most commonly diagnosed liver cancer. Besides advances in diagnosis and promising results of pre-clinical studies, HCC remains a highly lethal disease. In many cases, HCC is an effect of chronic liver inflammation, which leads to the formation of a complex tumor microenvironment (TME) composed of immune and stromal cells. The TME of HCC patients is a challenge for therapies, as it is involved in metastasis and the development of resistance. However, given that the TME is an intricate system of immune and stromal cells interacting with cancer cells, new immune-based therapies are being developed to target the TME of HCC. Therefore, understanding the complexity of the TME in HCC will provide new possibilities to design novel and more effective immunotherapeutics and combinatorial therapies to overcome resistance to treatment. In this review, we describe the role of inflammation during the development and progression of HCC by focusing on TME. We also describe the most recent therapeutic advances for HCC and possible combinatorial treatment options.

    Original languageEnglish
    Article number3778
    Number of pages22
    JournalInternational Journal of Molecular Sciences
    Volume23
    Issue number7
    DOIs
    Publication statusPublished - Apr-2022

    Keywords

    • hepatocellular carcinoma
    • tumor microenvironment
    • cancer therapy
    • immunotherapies
    • SINUSOIDAL ENDOTHELIAL-CELLS
    • ATEZOLIZUMAB PLUS BEVACIZUMAB
    • NATURAL-KILLER-CELLS
    • CD8(+) T-CELLS
    • KUPFFER CELLS
    • NONALCOHOLIC STEATOHEPATITIS
    • LYMPHOCYTE SUBSETS
    • HEPATIC STEATOSIS
    • POOR-PROGNOSIS
    • LIVER

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