Myeloid‐derived suppressor cells in gastrointestinal cancers: A systematic review

Hirbod-Mobarakeh, Armin; Mirghorbani, Masoud; Hajiju, Fatemeh; Marvi, Mahnaz; Bashiri, Kiandokht; Rezaei, Nima

doi:10.1111/jgh.13284

Cited by 15 publications

(14 citation statements)

References 48 publications

(203 reference statements)

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“…Abnormally increased MDSCs might contribute to poor prognosis of cancer patients. Several previous systematic reviews have evaluated the prognostic value of MDSCs in all types of solid tumors[33–35]. In these studies, the relationship between MDSCs and prognosis of HCC was also evaluated, but the number of relevant studies was very small.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of myeloid derived suppressor cell level in hepatocellular carcinoma: A systematic review and meta-analysis

Zhang

et al. 2019

PLoS ONE

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Background and aimsMany studies have investigated the association between the level of myeloid derived suppressor cells (MDSCs) and clinical features and prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. This systematic review and meta-analysis was conducted to summarize all available data and estimate the relationship.MethodsA comprehensive literature review was carried out using Medline, Embase and Web of Science database through December 2018 to identify relevant studies. The standardized mean difference (SMD) and the hazard ratio (HR) with 95% confidence interval (CI) were utilized for evaluating continuous outcomes and survival analysis, respectively. All statistical analyses were performed by STATA 14.0 software.ResultsA total of 13 studies with 1002 HCC patients were included in the meta-analysis. Overall, the proportion of MDSCs in HCC patients was higher than that in healthy controls (SMD = 4.49, 95% CI = 2.53–6.46, P<0.001), and patients with chronic liver disease (SMD = 3.41, 95% CI = 1.58–5.24, P<0.001). Subgroup analysis based on the phenotypes of MDSCs and geographical areas showed similar results. However, the frequency of MDSCs was not affected by the treatment with conventional approaches for HCC (SMD = -0.25, 95% CI = -0.57–0.06, P = 0.119). Moreover, increased MDSCs level was significantly associated with poorer overall survival (HR = 2.36, 95% CI = 1.70–3.29, P<0.001) and recurrence-free survival (HR = 2.72, 95% CI = 1.70–4.35, P<0.001), but not significantly correlated with any clinicopathological parameters.ConclusionThe results of this systematic review suggest that elevated MDSCs level appears to be associated with an increased risk for disease progression and poor prognosis for HCC.

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Section: Discussionmentioning

confidence: 99%

The prognostic value of myeloid derived suppressor cell level in hepatocellular carcinoma: A systematic review and meta-analysis

Zhang

et al. 2019

PLoS ONE

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“…They exist within a heterogeneous population of low‐density neutrophils (LDNs) that show altered functions as compared with normal‐density neutrophils (NDNs) . However, the mechanisms responsible for the expansion and polarization of these immunosuppressive cells are not fully understood .…”

Section: Introductionmentioning

confidence: 99%

Platelets contribute to the initiation of colitis‐associated cancer by promoting immunosuppression

Servais

Wéra

Epoh

et al. 2018

Journal of Thrombosis and Haemostasis

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Background Clinical and experimental evidence support a role for inflammation in the development of colorectal cancer, although the mechanisms are not fully understood. Beyond thrombosis and hemostasis, platelets are key actors in inflammation; they have also been shown to be involved in cancer. However, whether platelets participate in the link between inflammation and cancer is unknown. Objective To investigate the contribution of platelets and platelet-derived proteins to inflammation-elicited colorectal tumor development. Methods We used a clinically relevant mouse model of colitis-associated cancer. Platelet secretion and platelet reactivity to thrombin were assessed at each stage of carcinogenesis. We conducted an unbiased proteomic analysis of releasates of platelets isolated at the pretumoral stage to identify soluble factors that might act on tumor development. Plasma levels of the identified proteins were measured during the course of carcinogenesis. We then treated the mice with clopidogrel to efficiently inhibit platelet release reaction. Results At the pretumoral stage, hyperactive platelets constituted a major source of circulating protumoral serum amyloid A (SAA) proteins. Clopidogrel prevented the early elevation of the plasma SAA protein level, decreased colitis severity, and delayed the formation of dysplastic lesions and adenocarcinoma. Platelet inhibition hindered the expansion and function of immunosuppressive myeloid cells, as well as their infiltration into tumors, but increased the number of tissue CD8 T cells. Platelets and releasates of platelets from mice with cancer were both able to polarize myeloid cells towards an immunosuppressive phenotype. Conclusions Thus, platelets promote the initiation of colitis-associated cancer by enhancing myeloid cell-dependent immunosuppression. Antiplatelet agents may help to prevent inflammation-elicited carcinogenesis by restoring antitumor immunity.

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“…Specific subtypes of MDSC, monocytic (mMDSC) and granulocytic MDSC (gMDSC), can prevent the egress of activated CD8 T-cells into the tumor [1], downregulate TCR-zeta chain thus limiting T-cell activation [2], and impede T-cell differentiation [3]. Elevated levels of MDSC portend a poor prognosis or predict disease progression in many types of cancers [4–6]. High levels of MDSC in the peripheral blood of cancer patients prior to therapy is associated with a lack of or incomplete response to treatment for several cancers [7, 8].…”

Section: Introductionmentioning

confidence: 99%

TLR8 ligation induces apoptosis of monocytic myeloid-derived suppressor cells

Dang

Rutnam

Dietsch

et al. 2017

Journal of Leukocyte Biology

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Myeloid-derived suppressor cells (MDSCs) accumulate in tumors and the peripheral blood of cancer patients and demonstrate cancer-promoting activity across multiple tumor types. A limited number of agents are known to impact MDSC activity. TLR8 is expressed in myeloid cells.We investigated expression of TLR8 on MDSC and the effect of a TLR8 agonist, motolimod, on MDSC survival and function. TLR8 was highly expressed in monocytic MDSC (mMDSC) but absent in granulocytic MDSC (gMDSC). Treatment of human PBMC with motolimod reduced the levels of mMDSC in volunteers and cancer donors versus control (P < 0.001). Motolimod did not impact levels of gMDSC. The reduction of mMDSC was due to induced cell death by TLR8 ligation. Pretreatment of PBMC with a FAS neutralizing antibody inhibited motolimod-induced reduction of mMDSC (P < 0.001). Finally, we demonstrated that mMDSC impeded IL-2 secretion by CD3/CD28-activated T cells; IL-2 secretion was partially restored when cells were cocultured with motolimod (142 ± 36 pg/ml vs. 59 ± 13 pg/ml; P = 0.03). There is increasing evidence that MDSCs contribute to the progression of cancer by inhibiting tumor-directed T cells. TLR8 agonists may synergize with cancer immunotherapeutic approaches to enhance the antitumor effects of the adaptive immune response.

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Myeloid‐derived suppressor cells in gastrointestinal cancers: A systematic review

Abstract: In conclusion, results of this systematic review based on the available literature suggest that MDSC levels are of clinical relevancy and prognostic and predictive value.

Cited by 15 publications

References 48 publications

The prognostic value of myeloid derived suppressor cell level in hepatocellular carcinoma: A systematic review and meta-analysis

The prognostic value of myeloid derived suppressor cell level in hepatocellular carcinoma: A systematic review and meta-analysis

Platelets contribute to the initiation of colitis‐associated cancer by promoting immunosuppression

TLR8 ligation induces apoptosis of monocytic myeloid-derived suppressor cells

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