CXCL10/CXCR3 signaling mobilized-regulatory T cells promote liver tumor recurrence after transplantation

Li, Chang Xian; Ling, Chen; Shao, Yan; Xu, Aimin; Li, Xiangcheng; Ng, Kevin Tak‐Pan; Liu, Xiao Bing; Yuen, Yuen; Xiang, Qi; Liu, Hui; Liu, Jiang; Yeung, Oscar W.H.; Yang, Xinquan; Liu, Qing Sheng; Lam, Yeh; Zhai, Yuan; Lo, Chung Mau; Man, Kwan

doi:10.1016/j.jhep.2016.05.032

Cited by 112 publications

(79 citation statements)

References 43 publications

(59 reference statements)

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“…It has been reported that regulatory T-cells initiate recruitment and suppressive function via a CCL1 dependent pathway (23,24). In addition, the CXCR3 signaling directly induces the mobilization and recruitment of Tregs (25). Therefore, the Helios-1 may function as the transcription factor for regulatory T-cells by targeting the CCL1 and CXCR3 molecules.…”

Section: Discussionmentioning

confidence: 99%

Role of a non-canonical splice variant of the Helios gene in the differentiation of acute lymphoblastic leukemic T cells

Liu

et al. 2018

Oncol Lett

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Abstract. T-cell acute lymphoblastic leukemia is a hematopoietic malignant disease, which arises from a genetic defect in the T-cell maturation signaling pathway. As a result, it is necessary to identify the molecules that impact T-cell development and control lymphoid-lineage malignancy. The present study utilized Jurkat T lymphoblastic cells as a well-established approach for the investigation into the function of the non-canonical alternative splice variant of Helios for the in vitro study of T-cell differentiation and leukemogenesis. In the present study, the Jurkat T-cell lines with stable overexpression of the wild-type (Helios-1) or the non-canonical short isoform (Helios-Δ326-1431), were established. RNA microarray, reverse transcription-quantitative polymerase chain reaction and flow cytometry were used to assess changes in the gene expression profiles and to monitor the cell surface markers during T-cell differentiation. Multiple genes associated with T-cell differentiation and leukemogenesis were identified as being either activated or suppressed. In addition, the results indicated that the stable overexpression of the Helios isoforms stimulated the differentiation pathway of the T-lineage lymphoblastic cells. Therefore, these results suggest that full-length Helios-1 has a tumor suppressor-like and immunomodulatory role, in contrast to the oncogenic function of the non-canonical short isoform

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Section: Discussionmentioning

confidence: 99%

Role of a non-canonical splice variant of the Helios gene in the differentiation of acute lymphoblastic leukemic T cells

Liu

et al. 2018

Oncol Lett

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“…Marginal liver grafts are probably more susceptible to ischemia/reperfusion injury (IRI) after liver transplantation . Early phase liver graft injury is known to trigger a series of inflammatory cascades that consequentially activate several immune cells with important implications in graft injury and tumor recurrence …”

Section: Impact Of Liver Graft Injury On Cancer Recurrencementioning

confidence: 99%

“…Recently, increasing evidence demonstrated that inflammatory signaling cascades activated by graft injury orchestrated regional immune regulation and cancer recurrence. We reported that posttransplant inflammatory responses mobilize more circulatory regulatory T cells (Tregs), which promote late phase tumor recurrence after liver transplantation . More circulating Tregs together with the activation of chemokine (C‐X‐C motif) ligand 10 (CXCL10)/chemokine (C‐X‐C motif) receptor 3 (CXCR3) signaling can be detected in the recipients with a small‐for‐size liver graft and tumor recurrence.…”

Section: Impact Of Liver Graft Injury On Cancer Recurrencementioning

confidence: 99%

“…(10) Early phase liver graft injury is known to trigger a series of inflammatory cascades that consequentially activate several immune cells with important implications in graft injury and tumor recurrence. (11) On the other hand, LDLT has been considered as an alternative choice to relieve the liver graft shortage and to provide the timely transplantation for liver cancer patients. However, the liver graft from a living donor is usually a small-for-size graft for the recipient, which is also associated with a higher incidence of acute phase liver graft injury ( Figure 1).…”

Section: Impact Of Liver Graft Injury On Cancer Recurrencementioning

confidence: 99%

“…We reported that posttransplant inflammatory responses mobilize more circulatory regulatory T cells (Tregs), which promote late phase tumor recurrence after liver transplantation. (11) More circulating Tregs together with the activation of chemokine (C-X-C motif) ligand 10 (CXCL10)/chemokine (C-X-C motif) receptor 3 (CXCR3) signaling can be detected in the recipients with a small-for-size liver graft and tumor recurrence. In a mouse model, the knockout of CXCL10 significantly decreases hepatic recruitment of CXCR31 Tregs after hepatic IRI.…”

Section: Impact Of Liver Graft Injury On Cancer Recurrencementioning

confidence: 99%

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Recurrent malignancy: Are we pushing the envelope?

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2017

Liver Transpl

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Inducible Regulatory T Cell Predicts Efficacy of PD‐1 Blockade Therapy in Melanoma

Shen

et al. 2022

Advanced Therapeutics

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Metastatic melanoma is a lethal disease with poor prognosis. Here, a patient is being studied with metastatic uveal melanoma whose liver metastases have heterogeneous response to PD-1 inhibitor. The progressive disease (PD) lesion is found to have more than two times the abundance of inducible regulatory T cell (iTreg) compared with the complete response (CR) lesion. Based on public datasets, high abundance of pretreatment iTreg is found able to predict poor response to PD-1 inhibitor and is correlated with unfavorable prognosis of patients with advanced cutaneous melanoma receiving PD-1 blockade therapy. Further, based on single-cell RNA sequencing data, the ratio of iTregs to CD8 + T cells is found significantly increased from pretreatment to post-treatment status in nonresponders, while no such changes are found among responders. In nonresponders, iTreg cells have increased expression of IL-10 and maintained high expression of PRDM1. The top enriched pathway in iTregs includes Il6-Jak-Stat3 Signaling, Il2-Stat5 Signaling, and Glycolysis. A series of targeted or small molecule drugs predicted by iTreg specific genes are introduced. This study provides an insight into the immune suppressive role of iTreg in immunotherapy for melanoma.

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CXCL10/CXCR3 signaling mobilized-regulatory T cells promote liver tumor recurrence after transplantation

Abstract: There were positive correlation among tumor recurrence, circulating Tregs and liver graft injury after human transplantation for HCC patients. The knockout of CXCL10 decreased hepatic recruitment of CXCR3 Tregs and late phase tumor recurrence after hepatic IR injury.

Cited by 112 publications

References 43 publications

Role of a non-canonical splice variant of the Helios gene in the differentiation of acute lymphoblastic leukemic T cells

Role of a non-canonical splice variant of the Helios gene in the differentiation of acute lymphoblastic leukemic T cells

Recurrent malignancy: Are we pushing the envelope?

Inducible Regulatory T Cell Predicts Efficacy of PD‐1 Blockade Therapy in Melanoma

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