Progression on the Roles and Mechanisms of Tumor-Infiltrating T Lymphocytes in Patients With Hepatocellular Carcinoma

Zheng, Xin; Jin, Wenjie; Wang, Shanshan; Ding, Huiguo

doi:10.3389/fimmu.2021.729705

Cited by 73 publications

(46 citation statements)

References 113 publications

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“…Some traditional Chinese medicines serve an anti-tumor role in immunosuppressive tumor microenvironment through upregulating immune response [ 28 ]. Tumor-infiltrating lymphocytes, which can recognize tumor cells and provoke an anti-tumor response plays an active role in the survival of patients with hepatocellular carcinoma [ 29 ]. There are also reports the ratios of tumor‐infiltrating CD4 + /CD8 + are associated with the survival of the patients with HCC [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Taraxasterol prompted the anti-tumor effect in mice burden hepatocellular carcinoma by regulating T lymphocytes

et al. 2022

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Hepatocellular carcinoma (HCC) is a common digestive malignant tumor with high morbidity and mortality worldwide, however, the treatment of HCC and prognosis of patients are not optimistic, finding more effective treatments are imperative. Taraxacum officinale (L.) Weber ex F.H.Wigg is a perennial herb of compositae, and our study has demonstrated that Taraxacum officinale polysaccharide has certain anti-tumor effect on HCC cells. Taraxasterol (TS) is a natural product extracted from Taraxacum officinale with strong physiological, pharmacological and biological activities, but the effect of TS on HCC is yet to be determined. Therefore, the aim of this study is to explore the effect of dandelion sterol on HCC in vivo and in vitro. The results showed that TS significantly inhibited the proliferation, induced apoptosis and blocked cell cycle in HCC cell lines HepG2 and Huh7 cells in vitro. TS inhibited the tumor growth of H22 bearing mice and the expression of Ki67 in vivo. More importantly, TS regulated the immunity of H22 bearing mice by elevating the ratio of CD4+ T cells in spleen, and increasing the number of T cell infiltration in tumor tissue. Except immunomodulation, the mechanism of tumor growth inhibition may be related to the regulation of apoptosis related proteins and IL-6/STAT3 pathway. TS significantly inhibited the growth of HCC cells both in vitro and in vivo. The study would provide a theoretical basis for the new application of TS and the adjuvant treatment of malignant tumor with traditional Chinese medicine.

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Section: Discussionmentioning

confidence: 99%

Taraxasterol prompted the anti-tumor effect in mice burden hepatocellular carcinoma by regulating T lymphocytes

et al. 2022

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“…It has been reported that CD4+CD25+Foxp3+ regulatory T cells (Tregs) play a immunosuppressive role in TME which contributes to HCC initiation and progression ( 48 ). CD3+, CD8+, activated NKs, and Foxp3+ T cells were also found to have a suppression function in HCC ( 49 ). Several included literatures demonstrated altered T cell subpopulations in patients after CIK cell infusions ( 26 , 28 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Cellular Immunotherapy by Local Infusion for Liver Tumor: A Systematic Review and Meta-Analysis

Chen

Zhang

et al. 2022

Front. Oncol.

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BackgroundCellular immunotherapy has become a new and promising treatment for patients with liver tumor. However, as most immune cells are delivered by intravenous injection, the effect is limited and is likely to produce systemic toxicity. Here, the objective was to investigate the efficacy and safety of cellular immunotherapy by local infusion, which seems to be a promising approach and has not been well-studied.MethodsThe PubMed, Web of Science, Embase, and Cochrane Library databases were searched to obtain literature. The overall response rate (ORR), overall survival (OS) rates, and adverse events were investigated to evaluate the effectiveness and safety of locoregional therapy. The methodological quality of the articles was assessed using the methodological index for non-randomized studies (MINORS) score. The meta-analysis was performed using Stata 15.0.ResultsThe eligible 17 studies involved a total of 318 patients. The random-effects model demonstrated that the ORR of local cell infusion therapy was 48% (95% confidence interval [CI]: 26%–70%). The pooled OS rate was 94% (95% CI: 83%–100%) at 6 months, 87% (95% CI: 74%–96%) at 12 months, and 42% (95% CI: 16%–70%) at 24 months. Subgroup analyses suggested that minimally invasive treatment and absence of metastasis were significantly associated with better ORR. Fourteen studies reported a variety of adverse events related to cell therapy by local perfusion. The most common complications after regional infusion of immune cells were myelosuppression (66%), fever (50%), gastrointestinal toxicity (22%), hepatic dysfunction (15%), and pleural effusion and/or ascites (14%).ConclusionsImmune cell therapy through local perfusion is effective for patients with liver cancer, with manageable toxicity. It demonstrates better prognosis when combined with minimally invasive therapy. Considering the potential limitations, more randomized controlled trials are needed to provide solid evidence for our findings.

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“…T lymphocytes . Heterogeneous subsets of T cells, including cytotoxic CD8 + T lymphocytes (CTLs) and CD4 + CD25 + FoxP3 + T regulatory lymphocytes (Tregs), have been identified to infiltrate HCC tumors [ 46 , 47 ]. Whereas CTLs exhibit anti-tumorigenic properties, Tregs promote immunosuppression [ 48 ].…”

Section: Components Of the Tme In Hccmentioning

confidence: 99%

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

Sas

Cendrowicz

Weinhäuser

et al. 2022

IJMS

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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.

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Progression on the Roles and Mechanisms of Tumor-Infiltrating T Lymphocytes in Patients With Hepatocellular Carcinoma

Cited by 73 publications

References 113 publications

Taraxasterol prompted the anti-tumor effect in mice burden hepatocellular carcinoma by regulating T lymphocytes

Taraxasterol prompted the anti-tumor effect in mice burden hepatocellular carcinoma by regulating T lymphocytes

Efficacy and Safety of Cellular Immunotherapy by Local Infusion for Liver Tumor: A Systematic Review and Meta-Analysis

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

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