Regulatory T cells are associated with post-cryoablation prognosis in patients with hepatitis B virus-related hepatocellular carcinoma

Zhou, Lin; Fu, Junliang; Lu, Yinying; Fu, Baoyun; Wang, Chunping; An, Lihui; Wang, Xinzhen; Zeng, Zhen; Zhou, Chun‐Bao; Yang, Yongping; Wang, Fusheng

doi:10.1007/s00535-010-0243-3

Cited by 51 publications

(41 citation statements)

References 39 publications

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“…When the balance skews towards being Tregs-dominant, it may promote HCC progression. Our results further support the conclusions of other authors that tumor-infiltrating Tregs can predict the prognosis of HCC patients [20,46] . Thus, high-density intratumoral Tregs create a generalized immunosuppressive microenvironment and contribute to tumor cells escaping immune surveillance [47].…”

Section: Discussionsupporting

confidence: 82%

Tumor-Infiltrating FoxP3+ Tregs and CD8+ T Cells Affect the Prognosis of Hepatocellular Carcinoma Patients

Huang¹,

Wang²,

Wang³

et al. 2012

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Purpose: Tumor-infiltrating lymphocytes are considered to represent a host immune response against tumor. This study was carried out to analyze the effect of both FoxP3+ regulatory T cells (Tregs) and CD8+ T lymphocytes in prognostic value of hepatocellular carcinoma (HCC) patients. Methods: Expressions of FoxP3, CD4, CD8 and CD34 in patient-matched tumors and peritumoral tissues were assessed by immunohistochemistry for 54 HCC patients. The prognostic effect of groups with high and low numbers was evaluated by the Kaplan-Meier and Cox model analysis using median values as a cutoff. Results: Compared with the corresponding peritumoral tissue, the density of intratumoral Tregs was significantly higher, while the density of intratumoral CD8+ T cells was lower (p < 0.001 and p = 0.013, respectively). In addition, tumor-infiltrating Tregs were positively correlated with microvessel density in tumors (r = 0.334, p = 0.020). The high intratumoral Tregs density group showed a significantly lower survival rate (overall survival, p = 0.018; disease-free survival, p = 0.029). Multivariate Cox analysis revealed that intratumoral Tregs density was an independent prognostic factor for HCC. Conclusions: Tumor-infiltrating Tregs may promote HCC progression by fostering angiogenesis and decreasing CD8+ T cells. High tumor-infiltrating Tregs are thought to be an unfavorable prognostic indicator for HCC.

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Section: Discussionsupporting

confidence: 82%

Tumor-Infiltrating FoxP3+ Tregs and CD8+ T Cells Affect the Prognosis of Hepatocellular Carcinoma Patients

Huang¹,

Wang²,

Wang³

et al. 2012

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“…CD4 1 CD25 1 Foxp3 1 Tregs had an adverse effect on the prognosis of many tumors, 44 including HCC. 45 In the current study, we found a decrease of CD4 1 CD25 1 Foxp3 1 Tregs in tumors of mice that were vaccinated with Lmdd-CD24. In ELISPOT and LDH-release assays, Lmdd-CD24 vaccine increased the number of CD8 1 T cells isolated from TILs.…”

Section: Discussionsupporting

confidence: 57%

Attenuated Listeria monocytogenes as a cancer vaccine vector for the delivery of CD24, a biomarker for hepatic cancer stem cells

Hou

Zhe

et al. 2014

Cell Mol Immunol

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Attenuated Listeria monocytogenes (LM) is a promising candidate vector for the delivery of cancer vaccines. After phagocytosis by antigen-presenting cells, this bacterium stimulates the major histocompatibility complex (MHC)-I and MHC-II pathways and induces the proliferation of antigen-specific T lymphocytes. A new strategy involving genetic modification of the replication-deficient LM strain DdalDdat (Lmdd) to express and secrete human CD24 protein has been developed. CD24 is a hepatic cancer stem cell biomarker that is closely associated with apoptosis, metastasis and recurrence of hepatocellular carcinoma (HCC). After intravenous administration in mice, Lmdd-CD24 was distributed primarily in the spleen and liver and did not cause severe organ injury. Lmdd-CD24 effectively increased the number of interferon (IFN)-c-producing CD8 1 T cells and IFN-c secretion. Lmdd-CD24 also enhanced the number of IL-4-and IL-10-producing T helper 2 cells. The efficacy of the Lmdd-CD24 vaccine was further investigated against Hepa1-6-CD24 tumors, which were inguinally inoculated into mice. Lmdd-CD24 significantly reduced the tumor size in mice and increased their survival. Notably, a reduction of T regulatory cell (Treg) numbers and an enhancement of specific CD8 1 T-cell activity were observed in the tumor-infiltrating lymphocytes (TILs). These results suggest a potential application of the Lmdd-CD24 vaccine against HCC.

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“…Our search strategy yielded 573 primary articles, of which 16 were eventually identified fulfilling the eligibility criteria (Fu et al, 2007;Gao et al, 2007;Kobayashi et al, 2007;Sasaki et al, 2008;Cai et al, 2009;Ju et al, 2009a;2009b;Zhou et al, 2009;2010;Chen et al, 2011;Shen et al, 2011;Huang et al, 2012;Mathai et al, 2012;Wang et al, 2012;Lin et al, 2013) (Fig. 1).…”

Section: Study Characteristicsmentioning

confidence: 99%

Prognostic significance of regulatory T lymphocytes in patients with hepatocellular carcinoma

Zhang

Qian

Zheng

2016

J. Zhejiang Univ. Sci. B

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Abstract:We investigated the prognostic role of regulatory T cells (Tregs) in patients with hepatocellular carcinoma (HCC). Relevant evidence regarding prognostic significance of Tregs was systematically searched in MEDLINE and Embase databases. A meta-analysis was performed to compare survival in patients with high or low Tregs level (either in peripheral blood or tumor). Eighteen studies were identified that fulfilled for the eligibility criteria and were included for data synthesis. Our pooled hazard ratios (HRs) demonstrated that increased Tregs intratumoral accumulation was significantly associated with worse overall survival (HR=2.04, 95% confidence interval (CI): 1.72-2.42) and diseasefree survival (HR=1.82, 95% CI: 1.58-2.09). Three studies evaluated the role of Tregs in peripheral blood, and all of them showed that increased peripheral Tregs correlated with shortened disease-free and overall survival. Collectively, our results showed that the increased Tregs count is tightly associated with the shortened survivals. Its measurement in either primary tumor or even circulation might be a candidate marker of prognostic significance in HCC patients.

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Regulatory T cells are associated with post-cryoablation prognosis in patients with hepatitis B virus-related hepatocellular carcinoma

Abstract: Treg variation is associated with tumor regression or progression in HCC following cryoablation and may be used as a marker to estimate HCC progression.

Cited by 51 publications

References 39 publications

Tumor-Infiltrating FoxP3+ Tregs and CD8+ T Cells Affect the Prognosis of Hepatocellular Carcinoma Patients

Tumor-Infiltrating FoxP3+ Tregs and CD8+ T Cells Affect the Prognosis of Hepatocellular Carcinoma Patients

Attenuated Listeria monocytogenes as a cancer vaccine vector for the delivery of CD24, a biomarker for hepatic cancer stem cells

Prognostic significance of regulatory T lymphocytes in patients with hepatocellular carcinoma

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