Myeloid-derived suppressor cells correlate with patient outcomes in hepatic arterial infusion chemotherapy for hepatocellular carcinoma

Mizukoshi, Eishiro; Yamashita, Tatsuya; Arai, Kuniaki; Terashima, Toshio; Kitahara, Masaaki; Nakagawa, Hidetoshi; Iida, Noriho; Fushimi, Kazumi; Kaneko, Shuichi

doi:10.1007/s00262-016-1837-2

Cited by 60 publications

(39 citation statements)

References 30 publications

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“…26 mMDSCs accumulate in hepatocellular carcinoma (HCC), and a higher mMDSC frequency (more than 30.5% of CD14 + cells) indicates a shorter survival of HCC patients treated with hepatic arterial infusion chemotherapy. 13 There are significantly more mMDSCs in the liver in patients with non-alcoholic fatty liver disease than in HCs. 27 Taken together, the data indicate that gMDSCs are increased in ALD patients and associated with disease progression.…”

Section: Discussionmentioning

confidence: 95%

“…The frequencies of peripheral and intrahepatic mMDSCs correlate with liver inflammatory injury and viral load in chronic viral hepatitis and are associated with disease severity and prognosis in primary biliary cholangitis . mMDSCs accumulate in hepatocellular carcinoma (HCC), and a higher mMDSC frequency (more than 30.5% of CD14 + cells) indicates a shorter survival of HCC patients treated with hepatic arterial infusion chemotherapy . There are significantly more mMDSCs in the liver in patients with non‐alcoholic fatty liver disease than in HCs .…”

Section: Discussionmentioning

confidence: 99%

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Granulocytic myeloid‐derived suppressor cell population increases with the severity of alcoholic liver disease

Gao

Huang

Sun

et al. 2018

J Cellular Molecular Medi

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Alcoholic liver disease ( ALD ) is a progressive liver disease that can cause a series of complications, including cirrhosis, liver failure and hepatocellular carcinoma. Granulocytic myeloid‐derived suppressor cell ( gMDSC ) populations have been observed to expand in various liver diseases and to inhibit innate and adaptive immunity in patients with liver disease. However, the characteristics of gMDSC s in patients with ALD have not been studied. We studied 24 healthy controls ( HC s) and 107 patients with ALD and found an accumulation of gMDSC s in the peripheral blood of patients with alcoholic liver cirrhosis ( ALC ). Furthermore, ALC patients with a poor prognosis displayed a significant increase in peripheral gMDSC s and showed an increased capacity for arginase I production compared to HC s. In contrast, plasma arginase I levels in ALC patients were negatively correlated with total bilirubin and international normalized ratio, two key parameters of liver damage. Importantly, gMDSC s accumulated in the livers of ALC patients, and the frequency of liver gMDSC s significantly correlated with that of peripheral gMDSC s. In addition, gMDSC enrichment in vitro significantly inhibited the function of natural killer ( NK ) cells, perhaps preventing the NK ‐induced apoptosis of hepatic stellate cells. In summary, increased peripheral and intrahepatic gMDSC populations are present in patients with ALC and may contribute to enhancing the severity of liver cirrhosis.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Granulocytic myeloid‐derived suppressor cell population increases with the severity of alcoholic liver disease

Gao

Huang

Sun

et al. 2018

J Cellular Molecular Medi

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“…Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target and a prognostic factor for many malignant diseases, especially for hepatocellular carcinoma (HCC) [1–6]. However, target agents on MDSC have not display promising efficacy for HCC patients.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil count is associated with myeloid derived suppressor cell level and presents prognostic value for hepatocellular carcinoma patients

Xing

Lei

et al. 2017

Oncotarget

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Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for multiple cancers. However, target agents on MDSC have not display promising efficacy. One of the critical reasons shall be less optimal patient selection. In the present study, we aimed to identify clinical parameters relevant to MDSC level in hepatocellular carcinoma (HCC) patients for future MDSC targeted therapy. In the present study, a series of 55 HCC patients (testing group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC). As a result, we found that MDSC level was increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p < 0.0001). The monocytes (r2 = 0.2875, p < 0.0001), neutrophils (r2 = 0.3630, p < 0.0001) and platelet counts (r2 = 0.0828, p = 0.0331) in circulation was positively associated with MDSC level. Then, the prognostic value of the above predictors was determined in a retrospective database of 255 HCC patients (validation group). The baseline characteristics of testing and validation group were similar. Multivariate analysis by Cox regression revealed that neutrophil count was an independent predictor for overall survival (OS) (p = 0.000, HR 1.065, 95% CI 1.028–1.103), with the rest parameters failed to reach a significant result. In summary, the present study firstly identified blood neutrophil counts was a predictor of MDSC level in PBMC for HCC patients. And, patients with higher neutrophil count level might be the optimal patient subgroup for MDSC targeted therapy.

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“…(7) Myeloid-derived suppressor cells (MDSCs) have been shown to accumulate in the tumor, promote an immunosuppressive environment, and correlate with patient outcome. (8)(9)(10) Similarly, surgery may shift the balance between a proinflammatory T-helper 1 phenotype toward an immunosuppressive T-helper 2 phenotype, which may aid in promoting tumor proliferation and metastasis. (11,12) Therefore, one can postulate if adding an immunotherapy after surgery could in fact lead to an improved RFS by inhibiting immune-related protumor effects.…”

Section: Immune Landscape Of the Livermentioning

confidence: 99%

Adjuvant Treatment of Hepatocellular Carcinoma: Prospect of Immunotherapy

2019

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Although patients undergo procedures with curative intent for early-stage hepatocellular carcinoma (HCC), up to 70% of patients may have disease recurrence in the liver at 5 years. Thus far, no therapy has proven to be effective in the adjuvant setting. Here, we discuss the application of immune-based therapies in the adjuvant setting for HCC, focusing on the underlying rationale for immunotherapies, which patients may benefit from an immune-based therapy, and what type of immune therapy should be implemented.

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Myeloid-derived suppressor cells correlate with patient outcomes in hepatic arterial infusion chemotherapy for hepatocellular carcinoma

Cited by 60 publications

References 30 publications

Granulocytic myeloid‐derived suppressor cell population increases with the severity of alcoholic liver disease

Granulocytic myeloid‐derived suppressor cell population increases with the severity of alcoholic liver disease

Neutrophil count is associated with myeloid derived suppressor cell level and presents prognostic value for hepatocellular carcinoma patients

Adjuvant Treatment of Hepatocellular Carcinoma: Prospect of Immunotherapy

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