The Prognostic and Clinicopathological Significance of Tumor-Associated Macrophages in Patients with Gastric Cancer: A Meta-Analysis

Yin, Saifu; Huang, Jinyu; Li, Zhan; Zhang, Junyan; Luo, Jiazi; Lu, Chun‐Yang; Xu, Hao; Xu, Hui

doi:10.1371/journal.pone.0170042

Cited by 95 publications

(74 citation statements)

References 53 publications

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“…Immune surveillance evasion reflects the immune system’s failure to detect and eradicate tumor cells, allowing cancer to develop and spread . It has been shown in different tumor models that higher infiltration by neutrophils and macrophages in the tumor microenvironment is associated with worse oncological outcomes . On the contrary, higher lymphocyte infiltration is associated with better outcomes …”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] It has been shown in different tumor models that higher infiltration by neutrophils and macrophages in the tumor microenvironment is associated with worse oncological outcomes. [4][5][6][7] On the contrary, higher lymphocyte infiltration is associated with better outcomes. 8 At a systemic level, the same correlations have been studied in the peripheral blood.…”

Section: Introductionmentioning

confidence: 99%

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Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer

Valero

Zanoni

McGill

et al. 2019

Cancer

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Background Inflammation and immune surveillance evasion are cancer hallmarks. Peripheral blood leukocytes (PBLs) represent both. The aim of the current study was to examine PBLs as predictors of outcomes in oral cavity squamous cell carcinoma (OSCC), and to find specific cutoffs with the goal of including PBLs as host factor in patients' preoperative risk assessment. Methods Previously established head and neck squamous cell carcinoma (HNSCC) cutoffs were examined in an independent cohort of 1369 OSCC patients. Then optimal OSCC cutoffs were found and validated in the subset of patients with OSCC (n = 119) from the external HNSCC cohort. The PBLs analyzed were neutrophils, monocytes, and lymphocytes individually, the neutrophil‐to‐lymphocyte ratio (NLR), and a combined index using all PBLs called Systemic Inflammation Response Index (SIRI). Results All parameters were significant predictors of survival using the previous cutoffs. However, OSCC cutoffs stratified survival outcomes better. Considering neutrophils ≤4.8 × 109/L as reference, patients with 4.8–9.1 × 109/L neutrophils had 1.536 times higher risk of death (95% CI, 1.295‐1.822), and patients with ≥9.1 × 109/L had 3.076 times higher risk (95% CI: 2.170‐4.360). All PBLs maintained independent prognostic capacity in multivariable analysis. Neutrophils, NLR, and SIRI were significant predictors of survival when validating OSCC cutoffs in the external validation cohort. Conclusions Pretreatment peripheral blood neutrophils, NLR, and SIRI are the most robust independent predictors of overall survival among all PBLs in OSCC. The authors report externally validated cutoffs that demonstrate the feasibility of including PBLs as host features in the preoperative prognostication of OSCC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer

Valero

Zanoni

McGill

et al. 2019

Cancer

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“…Most solid tumours include a variety of immune cells such as regulatory T cells, myeloid‐derived suppressor cells and tumour‐associated macrophages (TAM) that can suppress CTL functions . Among these cells, TAM is one of the most abundant cell types in solid tumours and their infiltration into the tumour associates with poor prognosis in most solid tumours . Furthermore, macrophages isolated from mouse and human solid tumours can directly suppress T‐cell responses and NK cell cytotoxicity in vitro .…”

Section: Introductionmentioning

confidence: 99%

“…6,7 Among these cells, TAM is one of the most abundant cell types in solid tumours 8 and their infiltration into the tumour associates with poor prognosis in most solid tumours. [9][10][11][12][13][14] Furthermore, macrophages isolated from mouse and human solid tumours can directly suppress T-cell responses 15,16 and NK cell cytotoxicity 17,18 in vitro. It is also reported that depletion of TAM enhances CD8 + Tcell-mediated antitumour immunity under treatment with chemotherapy in a mouse model of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Macrophage targeting: opening new possibilities for cancer immunotherapy

2018

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SummaryTumour‐infiltrating immune cells regulate tumour development and progression either negatively or positively. For example, cytotoxic lymphocytes (CTL) such as CD8+ T and natural killer (NK) cells can recognize and eliminate cancer cells, and thereby restrict the tumour growth and metastasis, if they exert full cytotoxicity. In contrast, tumour‐infiltrating myeloid cells such as tumour‐associated macrophages (TAM) promote the expansion and dissemination of cancer cells depending on their functional states. Given the tumour‐killing ability of CTL, the augmentation of CTL‐induced antitumour immune reactions has been considered as an attractive therapeutic modality for lethal solid tumours and several promising strategies have emerged, which include immune checkpoint inhibitors, cancer vaccines and adoptive CTL transfer. These immunotherapies are now tested in clinical trials and have shown significant antitumour effects in patients with lymphoma and some solid tumours such as melanoma and lung cancer. Despite these encouraging results, these therapies are not efficient in a certain fraction of patients and tumour types with tumour cell‐intrinsic mechanisms such as impaired antigen presentation and/or tumour cell‐extrinsic mechanisms including the accumulation of immunosuppressive cells. Several animal studies suggest that tumour‐infiltrating myeloid cells, especially TAM, are one of the key targets to improve the efficacy of immunotherapies as these cells can suppress the functions of CD8+ T and NK cells. In this review, we will summarize recent animal studies regarding the involvement of TAM in the immune checkpoint, cancer vaccination and adoptive CTL transfer therapies, and discuss the therapeutic potential of TAM targeting to improve the immunotherapies.

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“…Despite the above cited examples of Treg cell suppression by polyphenols, other reports have demonstrated absence of effects on Treg cells in response to polyphenol administration either in vitro or in vivo [194,195]. As far as TAMs are concerned, these cells resemble M2 macrophages which promote tumor progression [196]. Strong evidence has been provided on the ability of RES to inhibit TAM activation via suppression of STAT3.…”

Section: Cancermentioning

confidence: 99%

Recent Advances on the Anti-inflammatory and Anti-oxidant properties of Red Grape Polyphenols: In Vitro and in Vivo Studies

Magrone¹,

Magrone²,

Russo³

et al. 2019

Preprint

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In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.

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The Prognostic and Clinicopathological Significance of Tumor-Associated Macrophages in Patients with Gastric Cancer: A Meta-Analysis

Cited by 95 publications

References 53 publications

Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer

Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer

Macrophage targeting: opening new possibilities for cancer immunotherapy

Recent Advances on the Anti-inflammatory and Anti-oxidant properties of Red Grape Polyphenols: In Vitro and in Vivo Studies

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