Use of gemcitabine- (Gem) and fluropyrimidine (FP)-based chemotherapy to reduce myeloid-derived suppressor cells (MDSCs) in pancreatic (PC) and esophagogastric cancer (EGC).

Gabitass, RF; Annels, NE; Crawshaw, James; Pandha, H.; Middleton, G. W.

doi:10.1200/jco.2011.29.15_suppl.2588

Cited by 14 publications

(10 citation statements)

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“…In addition, immune suppression was closely associated with the Th2-dominant condition. Previous studies suggested that the MDSC levels may decrease following administration of chemotherapeutic or certain anti-inflammatory agents (15,27). Therefore, the regulation of MDSC levels using these strategies may facilitate anti-ATC treatment, including immunotherapy.…”

Section: Discussionmentioning

confidence: 98%

“…Suppressive myeloid cells were previously described in patients with cancer (10,11), although their functional significance in the immune system has only recently been evaluated. Accumulating evidence (12)(13)(14)(15) suggests that a population of cells with suppressive activity, referred to as myeloid-derived suppressor cells (MDSCs), may contribute to the negative regulation of immune responses during cancer and other diseases. We previously characterized circulating levels of MDSCs in patients with various types of malignant diseases, including patients with thyroid cancer (16).…”

Section: Introductionmentioning

confidence: 99%

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Immunosuppression involving increased myeloid-derived suppressor cell levels, systemic inflammation and hypoalbuminemia are present in patients with anaplastic thyroid cancer

Suzuki

Shibata

Gonda

et al. 2013

Molecular and Clinical Oncology

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Anaplastic thyroid carcinoma (ATC) is one of the most aggressive neoplasms in humans and myeloid-derived suppressor cells (MDSCs) contribute to the negative regulation of immune responses in the context of cancer and inflammation. In order to investigate the pathophysiology of thyroid cancer, peripheral blood mononuclear cells (PBMCs) were obtained from 49 patients with thyroid cancer, 18 patients with non-cancerous thyroid diseases and 22 healthy volunteers. The MDSC levels were found to be higher in patients with any type of thyroid cancer (P<0.05), patients with ATC (P<0.001) and patients with medullary thyroid carcinoma (P<0.05), when compared to patients with non-cancerous thyroid diseases. The MDSC levels were also higher in patients with stage III-IV thyroid cancer compared to those in patients with non-cancerous thyroid diseases (P<0.05). The stimulation index (SI) of phytohemagglutinin (PHA)-induced lymphocyte blastogenesis was significantly lower, the C-reactive protein (CRP) levels were significantly higher and the serum albumin levels were significantly lower in patients with ATC compared to those in patients with non-cancerous thyroid diseases. The SI was significantly lower in stage III and IV thyroid cancer compared to that in non-cancerous thyroid disease (P<0.05). Furthermore, the CRP levels were higher and the concentration of albumin was lower in stage IV thyroid cancer compared to those in non-cancerous thyroid disease (P<0.05). Patients with thyroid carcinoma were then classified into one of two groups according to a %PBMC of MDSC cut-off level of 1.578, which was the average %PBMC of MDSC of patients with any type of thyroid carcinoma. In patients with higher MDSC levels, the production of CRP and interleukin (IL)-10 was significantly higher (P<0.05) and the albumin levels were significantly lower (P<0.05) compared to those in patients with lower MDSC levels. These data indicate that MDSCs are increased in patients with ATC. Furthermore, these patients exhibited suppression of cell-mediated immune responses, chronic inflammation and nutritional impairment.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Immunosuppression involving increased myeloid-derived suppressor cell levels, systemic inflammation and hypoalbuminemia are present in patients with anaplastic thyroid cancer

Suzuki

Shibata

Gonda

et al. 2013

Molecular and Clinical Oncology

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“…19 Similarly, in a cohort study of patients with melanoma (n ¼ 77, I-IV), taxane-based chemotherapy administration was shown to reduce the number of circulating MDSCs (HLA-DR À CD14 þ ). 98 Gabitass et al 99 have also reported a significant decrease in the number of circulating MDSCs in patients with pancreatic (n ¼ 16) and oesophagogastric (n ¼ 23) cancer post-treatment with gemcitabine-based chemotherapy (Po0.0001) . Of clinical interest, the decrease in MDSC numbers was also observed in patients at advanced stages.…”

Section: Potential Strategies To Target Mdscs In Human Cancersmentioning

confidence: 92%

Myeloid‐derived suppressor cells in cancer: recent progress and prospects

2013

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Immunosuppressive cells, mainly myeloid-derived suppressor cells (MDSCs) and T regulatory cells, downregulate antitumour immunity and cancer immunotherapy. MDSCs are a heterogeneous group of immature myeloid cells that negatively regulate the immune responses during tumour progression, inflammation and infection. Whilst there have been extensive laboratory investigations aimed at characterising the MDSC subsets in cancer, there remains a significant gap in our understanding of their phenotypical and functional heterogeneity. In this article, we review data concerning the phenotypical and functional role of MDSCs in cancers. Importantly, we analyse the value of MDSCs as a prognostic factor in various clinical settings and the possible therapeutic approaches towards elimination of their immunosuppressive activity and enhancement of beneficial antitumour immune responses. MDSCs promote tumour immune evasion by inhibiting T-cell responses, as well as by supporting tumour progression. Accumulation of MDSCs is associated with the progression of human cancers, and their elimination was shown to improve anti-tumour immune responses. Phenotypical characterisation of MDSCs has been poorly investigated in many human cancers and lacks comprehensive clinicopathological correlation data. Although the need for effective therapeutic agents to eliminate the MDSC suppressive effect is immense, their role has been examined only in a few clinical settings.

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“…Recent studies have identified myeloid-origin cells that are potent suppressors of tumor immunity and therefore a significant impediment to cancer immunotherapy. Suppressive myeloid cells were described three decades ago in patients with cancer (3,4), but their functional importance in the immune system has only recently been appreciated (5)(6)(7)(8). Indeed, accumulating evidence has now shown that a population of cells with suppressive activity [known as myeloid-derived suppressor cells (MDSCs)] contributes to the negative regulation of immune responses during cancer and other diseases.…”

Section: Introductionmentioning

confidence: 99%

Circulating myeloid-derived suppressor cells are increased and correlate to immune suppression, inflammation and hypoproteinemia in patients with cancer

et al. 2012

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Recent studies have identified myeloid-derived suppressor cells (MDSCs) that are potent suppressors of tumor immunity and therefore a significant impediment to cancer immunotherapy. It has been reported that MDSCs are generated by malignant diseases or inflammation. However, no systematic studies in patients have been described. In order to clinically characterize MDSCs, we tested PBMCs from patients with various types of cancer including cholangiocellular, hepatocellular and pancreatic carcinoma, esophageal, gastric and colorectal cancer, breast cancer and thyroid cancer, and GIST, and those from normal volunteers using flow cytometry analysis. A significant increase was seen in the percentages of MDSCs in PBMCs from patients compared with normal volunteers. Among these patients, MDSC level was higher in patients with cancer of the digestive system and patients with breast cancer compared with normal volunteers. MDSC level was significantly and inversely correlated to stimulation indices (SI) of PHA-blastogenesis of lymphocytes and serum concentration of total protein, and positively correlated to neutrophil count. MDSC percentage in patients with gastric and colorectal cancer was also significantly correlated to neutrophil count and inversely correlated with lymphocyte count, and showed highly significant correlation to neutrophil/lymphocyte rate (NLR). In patients with breast cancer, MDSC levels in preoperative patients was significantly increased compared to normal volunteers and significantly decreased in postoperative patients. Thus, it is clear that MDSCs are increased in patients with cancer and closely related to suppression of cell-mediated immune responses. These data also suggest that they are related to chronic inflammation and that their levels are increased further in the terminal stages of patients whose nutritional status is impaired as observed in hypoproteinemia. MDSC levels have also been shown to decrease after removal of tumors in patients with breast cancer.

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Use of gemcitabine- (Gem) and fluropyrimidine (FP)-based chemotherapy to reduce myeloid-derived suppressor cells (MDSCs) in pancreatic (PC) and esophagogastric cancer (EGC).

Cited by 14 publications

References 0 publications

Immunosuppression involving increased myeloid-derived suppressor cell levels, systemic inflammation and hypoalbuminemia are present in patients with anaplastic thyroid cancer

Immunosuppression involving increased myeloid-derived suppressor cell levels, systemic inflammation and hypoalbuminemia are present in patients with anaplastic thyroid cancer

Myeloid‐derived suppressor cells in cancer: recent progress and prospects

Circulating myeloid-derived suppressor cells are increased and correlate to immune suppression, inflammation and hypoproteinemia in patients with cancer

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