Reduction of FoxP3+ Tregs by an immunosuppressive protocol of rapamycin plus Thymalfasin and Huaier extract predicts positive survival benefits in a rat model of hepatocellular carcinoma

Zhou, Lin; Pan, Liao; Zheng, Yan; Zhang, Xinxue; Liu, Zhi-Jia; Meng, Xuan; Shi, Haida; Du, Gangjun; He, Qiang

doi:10.21037/atm.2020.03.129

Cited by 10 publications

(18 citation statements)

References 56 publications

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“…invasive neutrophils, [21][22][23][24] Foxp3 + regulatory T cells, 16,[25][26][27][28][29] and myeloid suppressor cells have become the research focus in the field of tumor immunity and tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

“…Literature research has confirmed that 14,27,29 infiltrated Foxp3 + Treg of preoperative peripheral blood and tissue were significantly negative correlation with the prognosis of patients with HCC and other solid tumor. In addition, the function of effector T cells can be reduced or the dysfunction of effector T cells can be caused by directly contact inhibition and indirectly secretion of inhibitory cytokines such as TGF-β and IL-10 of Foxp3 + Treg, 16,28,30 which can help tumor escape to promote proliferation and invasion.…”

Section: Discussionmentioning

confidence: 99%

“…7,20 In recent years, parallel with targeted therapy and biological immunotherapy, the mechanism study of tumor immune microenvironment of Abbreviations: HCC, hepatocellular carcinoma; IHC, immunohistochemistry. invasive neutrophils, [21][22][23][24] Foxp3 + regulatory T cells, 16,[25][26][27][28][29] and myeloid suppressor cells have become the research focus in the field of tumor immunity and tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

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PD-L1⁺NEUT, Foxp3⁺Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma

Zhou

Wang

Lyu

et al. 2021

Technol Cancer Res Treat

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Background: This presented study was aimed to evaluate the diagnostic and prognostic value of PD-L1+Neutrophils (PD-L1+NEUT) and neutrophil to lymphocyte ratio (NLR) based on our previous experience of Foxp3+Treg in transplantation. Methods: the NLR cutoff value of 1.79 was used to include 136 cases from the 204 patients with hepatocellular carcinoma (HCC) confirmed by clinical pathology, which were divided into highly-moderately and poorly differentiated HCC groups. The expressions of PD-L1+NEUT and Foxp3+Treg in peripheral blood and cancer tissue were detected with flow cytometry, meanwhile, PD-L1 and Foxp3 expressed in carcinoma and para-carcinoma tissues were marked by immunohistochemistry. Survival rates, including overall survival and disease-free survival, were calculated by the Kaplan–Meier curve and evaluated with the log-rank test. Finally, Cox risk regression model was used to analyze the independent risk factors for prognostic survival. Results: The level of PD-L1+NEUT, Foxp3+Treg, and NLR in peripheral blood of patients with poorly differentiated HCC were significantly increased (all P < .001). Both PD-L1+NEUT and NLR were positively correlated with Foxp3+Treg ( r = 0.479, P = .0017; r = 0.58, P < .0001). The level of PD-L1+NEUT and Foxp3+Treg as well as PD-L1 and Foxp3 in cancer tissue and patients with poorly differentiated HCC were obviously increased (all P < .01), respectively. Cox regression analysis indicated that PD-L1+NEUT, NLR, and Foxp3+Treg were independent risk factors for the prognosis ( P = .000, .000, .006) with a RR and 95%CI of 2.704-(2.155-3.393), 3.139-(2.361-4.173), 1.409-(1.105-1.798), respectively. Conclusion: PD-L1+NEUT, NLR, and Foxp3+Treg are independent risk factors for prognosis which maybe new marker of lower survival benefits.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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PD-L1⁺NEUT, Foxp3⁺Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma

Zhou

Wang

Lyu

et al. 2021

Technol Cancer Res Treat

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“…Based on this theory, we use animal models to find that RAPA can down-regulate Foxp3 + Treg mediated tumor immune escape through the mTOR pathway. High expression of mTOR and Treg was associated with a low rat survival time[ 46 ].…”

Section: Trends Of Rapa In Survival Benefits Of Transplant For Hccmentioning

confidence: 99%

“…Based on clinical research, we further found that RAPA-based therapy has an anti-tumor effect by reducing FoxP3 + Tregs and its inhibitory cytokines, and the application of PS-T enhances the anti-tumor effect of RAPA. This synergistic effect is mediated by the mTOR signal pathway[ 46 ]. To further verify the long-term efficacy and specific mechanism of the combination of RAPA and PS-T, it is necessary to perform multicenter, large sample randomized controlled trials.…”

Section: Trends Of Combined Therapy Of Rapa and Anti-tumor Drugs In Survival Benefits Of Transplant For Hccmentioning

confidence: 99%

Trends of rapamycin in survival benefits of liver transplantation for hepatocellular carcinoma

Zhao¹,

Liu²,

Zhou³

et al. 2021

WJGS

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The proportion of liver transplantation (LT) for hepatocellular carcinoma (HCC) has kept on increasing over the past years and account for 20%-40% of all LT. Post-transplant HCC recurrence is considered the most important factor affecting the long-term survival of patients. The use of different types of immunosuppressive agents after LT is closely associated with an increased risk for HCC recurrence. The most commonly used conventional immunosuppressive drugs include the calcineurin inhibitors tacrolimus (FK506) and mammalian target of rapamycin inhibitor rapamycin (RAPA). Compared with tacrolimus, RAPA may carry an advantage in survival benefit because of its anti-tumor effects. However, no sufficient evidence to date has proven that RAPA could increase long-term recurrence-free survival and its anti-tumor mechanism of combined therapy remains incompletely clear. In this review, we will focus on recent advances in clinical application experience and basic research results of RAPA in patients undergoing LT for HCC to further guide the clinical practice.

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The potential therapeutic benefits of Huaier in digestive system cancer: Its chemical components, pharmacological applications and future direction

Tang,

Yi,

Yang

et al. 2024

Journal of Functional Foods

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Reduction of FoxP3+ Tregs by an immunosuppressive protocol of rapamycin plus Thymalfasin and Huaier extract predicts positive survival benefits in a rat model of hepatocellular carcinoma

Cited by 10 publications

References 56 publications

PD-L1⁺NEUT, Foxp3⁺Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma

PD-L1⁺NEUT, Foxp3⁺Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma

Trends of rapamycin in survival benefits of liver transplantation for hepatocellular carcinoma

The potential therapeutic benefits of Huaier in digestive system cancer: Its chemical components, pharmacological applications and future direction

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Reduction of FoxP3+ Tregs by an immunosuppressive protocol of rapamycin plus Thymalfasin and Huaier extract predicts positive survival benefits in a rat model of hepatocellular carcinoma

Cited by 10 publications

References 56 publications

PD-L1+NEUT, Foxp3+Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma

PD-L1+NEUT, Foxp3+Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma

Trends of rapamycin in survival benefits of liver transplantation for hepatocellular carcinoma

The potential therapeutic benefits of Huaier in digestive system cancer: Its chemical components, pharmacological applications and future direction

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Product

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PD-L1⁺NEUT, Foxp3⁺Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma

PD-L1⁺NEUT, Foxp3⁺Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma