Prognostic significance of CD68+ and CD163+ tumor associated macrophages in head and neck squamous cell carcinoma: A systematic review and meta-analysis

Troiano, Giuseppe; Caponio, Vito Carlo Alberto; Adipietro, Iolanda; Tepedino, Michele; Santoro, Raffaela; Laino, Luigi; Russo, Lucio Lo; Cirillo, Nicola; Muzio, Lorenzo Lo

doi:10.1016/j.oraloncology.2019.04.019

Cited by 128 publications

(120 citation statements)

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“…At the same time, the prognostic significance of CD68 + infiltration in relation to other clinical endpoints could not be demonstrated. This finding is in line with the conclusions of the meta-analysis presented by Troiano et al [30], taking into account the results of 17 studies conducted on 1,528 patients with oral cancer, which excluded the prognostic significance of CD68 + infiltrates in this group of cancers and confirmed the usefulness of M2-like macrophage infiltrates assessment in the tumour stroma as an adverse prognostic factor. The results presented by us also indicate the usefulness of the CD163 + infiltration assessment in the tumour stroma as a negative prognostic factor in regard to the LRC, distant metastases-free survival and OS in the group of HPV-negative patients.…”

Section: Discussion/conclusionsupporting

confidence: 91%

“…As we know this is the first publication covering such a homogeneous group of patients with a comparable number of HPV-positive and HPV-negative cases and one of the few in which the HPV double-detection algorithm was used. Most of the publications in which the intensity of macrophage infiltration within head and neck tumours was analysed concerned locations in the oral cavity [30] or other locations outside the oropharynx [31], where HR-HPV status was unknown. Due to the low frequency of HR-HPV infections in the 2.5-4% range in these anatomical sites, it can be assumed that the results presented in them relate mainly to the HPV-negative population [32][33][34].…”

Section: Discussion/conclusionmentioning

confidence: 99%

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Infiltrates of M2-Like Tumour-Associated Macrophages Are Adverse Prognostic Factor in Patients with Human Papillomavirus-Negative but Not in Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma

et al. 2020

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Introduction: Human papillomavirus with a high oncogenic potential (HR-HPV) is responsible for more than a half of squamous cell carcinomas of the oropharynx. The HR-HPVdependent cases of this tumour have a better prognosis compared to the HR-HPV-negative cases, despite the usually more advanced disease at the time of diagnosis. In addition to genetic and epigenetic factors, the causes of this more favourable course of the disease are also seen in the participation of the tumour microenvironment, including the patient's immune system. Macrophages are one of the most important elements of the immunocompetent cells landscape that make up the tumour microenvironment. Traditionally, they are divided into 2 groups: inflammatory macrophages with the M1 phenotype and tumour-associated macrophages known as M2 phenotype macrophages. Objective: The aim of this study was to investigate the impact ated with higher rate of nodal failures and a shorter nodal control in both HR-HPV groups. In the group of HR-HPV-negative patients, heavy infiltration of CD163 + macrophages was associated with significantly shorter: loco-regional control (LRC), metastasis-free survival and overall survival (OS). These parameters and prognosis in patients with scanty CD163 + infiltration were similar to favourable outcomes in HR-HPV-positive patients. The relative risk of local-regional recurrence, distant metastases and disease-related death in HR-HPV-negative patients with intense CD163 + infiltrates was, respectively, 4.7, 5.4 and 5.7 compared to patients with scanty infiltrates. Conclusions: Tumours with a positive HR-HPV status demonstrate intense infiltrations of total pool M1/M2 and M2 macrophages. In the group of HPV-negative patients, intensive M1/M2 macrophage infiltrates correlate with higher risk of nodal failures, and intensive M2 infiltrates are an adverse prognostic factor for LRC, metastasis-free survival and OS.

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Section: Discussion/conclusionsupporting

confidence: 91%

Section: Discussion/conclusionmentioning

confidence: 99%

Infiltrates of M2-Like Tumour-Associated Macrophages Are Adverse Prognostic Factor in Patients with Human Papillomavirus-Negative but Not in Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma

et al. 2020

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“…Head and neck squamous cell carcinoma (HNSCC) is a member of highly aggressive tumors that involve the epithelium numerous anatomical sections, such as the oral cavity [151]. Zhang et al demonstrated that miR-144-3p, by targeting of ETS-1 and insulin receptor substrate 1 (IRS1) in laryngeal squamous cell carcinoma, led to the inhibition of metastasis and invasion of tumor cells.…”

Section: Mir-144 In Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

Kooshkaki

Rezaei

Rahmati

et al. 2020

IJMS

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MicroRNAs (miRNAs) are small and non-coding RNAs that display aberrant expression in the tissue and plasma of cancer patients when tested in comparison to healthy individuals. In past decades, research data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been confirmed that miRNAs can act either as oncogenes by silencing tumor inhibitors or as tumor suppressors by targeting oncoproteins. MiR-144s are located in the chromosomal region 17q11.2, which is subject to significant damage in many types of cancers. In this review, we assess the involvement of miR-144s in several cancer types by illustrating the possible target genes that are related to each cancer, and we also briefly describe the clinical applications of miR-144s as a diagnostic and prognostic tool in cancers.Int. J. Mol. Sci. 2020, 21, 2578 2 of 23 of a mRNA molecule [3]. MiRNAs indicate a new perspective in the study of cancers. More than 50% of miRNA genes were discovered to be located within the genomic regions that are involved in cancers, suggesting their role in human cancer pathogenesis. In pathological conditions, MiRNAs can negatively regulate gene expression and they are associated with tumor growth, apoptosis, invasion, and metastasis. In the past, several studies have indicated the ability of miRNAs in the inhibition of tumors as a critical option for the improvement of cancer therapy [4,5]. Tumor activator miRNAs, called oncomiRs, are overexpressed in various cancers. On the contrary, suppressive tumor miRNAs are underexpressed [6][7][8]. Among several miRNAs assessed, miR-144s seem to have a role in several cancers. These miRNAs are located in the chromosomal region 17q11.2, being significantly destroyed in many types of cancers. The predicted stem-loop structure of miR-144s recognized by the miRBase (http://mirbase.org/) is shown in Figure 1A. The miR-144 hairpin gives rise to the "guide strand" miR-144-5p and the sister "passenger" strand miR-144-3p ( Figure 1B).

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“…Immunostains were done on paraffin-embedded sections using the Ventana Discovery DAB Map System (Ventana, Illkirch, France), as previously described [9]. We assessed macrophages using CD68 (anti-CD68, DAKO IR613, dilution 1:2), CD163 for M2-like macrophages (anti-CD163, Abcam Ab74604, neat) and HLA-DR for M1-like macrophages (anti-HLA-DR, Abcam Ab20181 [TAL1B5], dilution 1:100) [14,[33][34][35], lymphocytes using CD8 for cytotoxic T cells (anti-CD8, DAKO M7103, dilution 1:100), CD4 for T helper cells (anti-CD4, Abcam Ab133616, dilution 1:100), FOXP3 for T regulatory cells (anti-FOXP3, Abcam Ab20034 [236 A/E7], dilution 1:50), CD20 for B lymphocytes (anti-CD20, DAKO M0755, dilution 1:300) and neutrophil elastase for neutrophils (anti-neutrophil elastase, Abcam Ab68672, dilution 1:100). To study endothelial cells we used the marker CD31 (anti-CD31, DAKO M0823, dilution 1:100), and we also took into consideration their location and morphology.…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

The role of the tumour microenvironment in the angiogenesis of pituitary tumours

Marques

Barry

Carlsen³

et al. 2020

Endocrine

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Purpose Angiogenesis has been studied in pituitary neuroendocrine tumours (PitNETs), but the role of the tumour microenvironment (TME) in regulating PitNET angiogenesis remains unknown. We aimed to characterise the role of TME components in determining the angiogenetic PitNET profile, focusing on immune cells and tumour-derived cytokines. Methods Immune cells were studied by immunohistochemistry in 24 human PitNETs (16 non-functioning-PitNETs (NF-PitNETs) and 8 somatotrophinomas): macrophages (CD68, CD163, HLA-DR), cytotoxic (CD8) and T helper (CD4) lymphocytes, regulatory T cells (FOXP3), B cells (CD20) and neutrophils (neutrophil elastase); endothelial cells were assessed with CD31. Five normal pituitaries (NP) were included for comparison. Microvessel density and vascular morphology were estimated with ImageJ. The cytokine secretome from these PitNETs were assessed on culture supernatants using a multiplex immunoassay panel. Results Microvessel density/area was higher in NP than PitNETs, which also had rounder and more regular vessels. NF-PitNETs had vessels of increased calibre compared to somatotrophinomas. The M2:M1 macrophage ratio correlated with microvessel area. PitNETs with more CD4+ T cells had higher microvessel area, while tumours with more FOXP3+ cells were associated with lower microvessel density. PitNETs with more B cells had rounder vessels. Of the 42 PitNET-derived cytokines studied, CCL2, CXCL10 and CX3CL1 correlated with microvessel density and vessel architecture parameters. Conclusions M2 macrophages appear to play a role in PitNET neovascularisation, while B, CD4+ and FOXP3+ lymphocytes, as well as non-cellular TME elements such as CCL2, CXCL10 and CX3CL1, may also modulate the angiogenesis of PitNETs.

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Prognostic significance of CD68+ and CD163+ tumor associated macrophages in head and neck squamous cell carcinoma: A systematic review and meta-analysis

Cited by 128 publications

References 41 publications

Infiltrates of M2-Like Tumour-Associated Macrophages Are Adverse Prognostic Factor in Patients with Human Papillomavirus-Negative but Not in Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma

Infiltrates of M2-Like Tumour-Associated Macrophages Are Adverse Prognostic Factor in Patients with Human Papillomavirus-Negative but Not in Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

The role of the tumour microenvironment in the angiogenesis of pituitary tumours

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