Therapeutic Values of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma: Facts and Hopes

Wang, Yijun; Zhang, Tongyue; Sun, Mengyu; Ji, Xiaoyu; Xie, Meng; Huang, Wenjie; Xia, Limin

doi:10.3390/cancers13205127

Cited by 22 publications

(10 citation statements)

References 124 publications

(173 reference statements)

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“…In conclusion, MDSCs have two main functions: on the one hand, it promotes tumor progression by inhibiting the anti-tumor function of T cells and NK cells; on the other hand, MDSCs also promote new angiogenesis and tumor cell invasion 53 . Previous studies have shown that MDSCs from HCC patients can inhibit the cytotoxicity and cytokine secretion of NK cells when cultured with NK cells in vitro 54 . MDSCs can express high levels of PD-L1, and can also recruit Tregs by expressing CD40.…”

Section: The Immune Network In Tme Of Hccmentioning

confidence: 98%

New insights into checkpoint inhibitor immunotherapy and its combined therapies in hepatocellular carcinoma: from mechanisms to clinical trials

Jin¹,

Qin²,

He³

et al. 2022

Int. J. Biol. Sci.

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Hepatocellular carcinoma (HCC) is one of the most lethal tumors in China and worldwide, although first-line therapies for HCC, such as atezolizumab and bevacizumab, have been effective with good results, the researches on new therapies have attracted much attention. With the deepening research on tumor immunology, the role and operation mechanism of immune cells in the tumor microenvironment (TME) of HCC have been explained, such as programmed cell death protein 1 (PD-1) binding to ligand could cause T cell exhaustion and reduce IFN-γ T cell secretion, cytotoxic T lymphocyte 4 (CTLA-4) and CD28 mediate immunosuppression by competing for B7 protein and disrupting CD28 signal transduction pathway, which also lays the foundation for the development and application of more new immune checkpoint inhibitors (ICIs). The biological behavior of various immune checkpoints has been proved in HCC, such as PD-1, programmed cell death ligand 1 (PD-L1), CTLA-4 and so on, leading to a series of clinical trials. Currently, FDA approved nivolumab, pembrolizumab and nivolumab plus ipilimumab for the treatment of HCC. However, the treatment of ICI has the disadvantages of low response rate and many side effects, so the combination of ICIs and various other therapies (such as VEGF or VEGFR inhibition, neoadjuvant and adjuvant therapy, locoregional therapies) has been derived. Further studies on immune checkpoint mechanisms may reveal new therapeutic targets and new combination therapies in the future.

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Section: The Immune Network In Tme Of Hccmentioning

confidence: 98%

New insights into checkpoint inhibitor immunotherapy and its combined therapies in hepatocellular carcinoma: from mechanisms to clinical trials

Jin¹,

Qin²,

He³

et al. 2022

Int. J. Biol. Sci.

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“…PMN-MDSCs are mainly enriched in TIME and generate large amounts of reactive oxygen species (ROS) to mediate T cell tolerance. However, M-MDSCs accumulate in peripheral blood expressing high levels of iNOS but releasing low ROS to suppress the immune response [ 85 ]. Emerging studies have shown that CAFs could promote the generation of MDSCs through paracrine manner.…”

Section: The Roles Of Cafs In Hcc Progressionmentioning

confidence: 99%

Advances of cancer-associated fibroblasts in liver cancer

2022

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Liver cancer is one of the most common malignant tumors worldwide, it is ranked sixth in incidence and fourth in mortality. According to the distinct origin of malignant tumor cells, liver cancer is mainly divided into hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Since most cases are diagnosed at an advanced stage, the prognosis of liver cancer is poor. Tumor growth depends on the dynamic interaction of various cellular components in the tumor microenvironment (TME). As the most abundant components of tumor stroma, cancer-associated fibroblasts (CAFs) have been involved in the progression of liver cancer. The interplay between CAFs and tumor cells, immune cells, or vascular endothelial cells in the TME through direct cell-to-cell contact or indirect paracrine interaction, affects the initiation and development of tumors. Additionally, CAFs are not a homogeneous cell population in liver cancer. Recently, single-cell sequencing technology has been used to help better understand the diversity of CAFs in liver cancer. In this review, we mainly update the knowledge of CAFs both in HCC and CCA, including their cell origins, chemoresistance, tumor stemness induction, tumor immune microenvironment formation, and the role of tumor cells on CAFs. Understanding the context-dependent role of different CAFs subsets provides new strategies for precise liver cancer treatment.

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“…MDSCs can be classified into two groups: monocytic and polymorphonuclear. The monocytic MDSCs inhibit T cell responses through the production of anti-inflammatory cytokines and nitric oxide, whereas the polymorphonuclear MDSCs suppress T cells by generating peroxynitrite, which nitrates T cell receptors to reduce their responsiveness to antigen-MHC complexes [ 24 , 25 , 26 ].…”

Section: The Immune Microenvironment Of Hccmentioning

confidence: 99%

Immunotherapeutic Approaches for Treating Hepatocellular Carcinoma

Shen

Chen

Pan

et al. 2022

Cancers

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Liver cancer is a life-threatening disease, and its incidence is increasing globally. The most common form of liver cancer is hepatocellular carcinoma (HCC). Approximately half of patients with HCC, especially those at advanced disease stages, receive systemic therapies, including the tyrosine kinase inhibitors sorafenib and lenvatinib. Over the past few years, immune checkpoint inhibitors (ICIs) have changed the landscape of HCC treatment. In particular, the combination therapy with atezolizumab (an anti-PD-L1 antibody) and bevacizumab (an anti-VEGF antibody) significantly improved survival benefits compared with sorafenib as a single agent, a finding that has stimulated further preclinical and clinical development of immunotherapeutic approaches for treating HCC. In addition to ICIs, oncolytic immunotherapy and adoptive T cell therapy have also emerged as immunotherapeutic strategies. A major challenge is that the tumor microenvironment of HCC is usually immunosuppressive, leading to immune escape and immunotherapy resistance. Hence, combination therapies that could sensitize HCC to immunotherapy have become a growing area of investigation. In this review, we summarize recent advances in HCC immuno-oncology and review immunotherapeutic strategies that are under development for treating HCC.

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Therapeutic Values of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma: Facts and Hopes

Cited by 22 publications

References 124 publications

New insights into checkpoint inhibitor immunotherapy and its combined therapies in hepatocellular carcinoma: from mechanisms to clinical trials

New insights into checkpoint inhibitor immunotherapy and its combined therapies in hepatocellular carcinoma: from mechanisms to clinical trials

Advances of cancer-associated fibroblasts in liver cancer

Immunotherapeutic Approaches for Treating Hepatocellular Carcinoma

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