High infiltration of CD68+ macrophages is associated with poor prognoses of head and neck squamous cell carcinoma patients and is influenced by human papillomavirus

Seminerio, Imelda; Kindt, Nadège; Descamps, Géraldine; Bellier, Justine; Lechien, Jérôme R.; Mat, Quentin; Pottier, Charles; Journé, Fabrice; Saussez, Sven

doi:10.18632/oncotarget.24306

Cited by 60 publications

(65 citation statements)

References 39 publications

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“…However, significantly more intense infiltration of both the total macrophage pool and M2-like macrophages was found in HR-HPV-positive tumours compared to HPVnegative ones. Similar observations were described in the work of Seminerio regarding the total macrophage pool [37] and by Ryu et al [38] in relation to M2-like macrophages. In the first study, the authors also showed the significance of CD68 + macrophage infiltrates in tumour tissue as an independent factor of poor prognosis in regard to relapse-free survival and OS.…”

Section: Discussion/conclusionsupporting

confidence: 88%

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: 88%

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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“…Our data fits with other studies that show that exposure of mice to CSE induces macrophage recruitment in lung tissues and lung tumors, and that these macrophages are polarized to a protumorigenic phenotype (55,56). In HNSCC, macrophages promote cell migration, invasion and lymph node metastasis in in vitro and in vivo models, and are associated with worse outcome in patients (53,57,58). Moreover, studies show the correlation between the density of CAFs and TAMs with poor outcome in HNSCC (59,60).…”

Section: Discussionsupporting

confidence: 91%

“…HNSCC has abundant immune infiltration (51). CD68, a macrophage marker, is abundantly expressed in HNSCC tumor tissue, as opposed to normal tissue, and correlates with aggressive behavior, lymph node metastasis, increased incidence of extracapsular spread, and overall worse survival (52)(53)(54). We determined the effects of fibroblast CSE exposure on macrophage recruitment.…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Induces Metabolic Reprogramming of the Tumor Stroma in Head and Neck Squamous Cell Carcinoma

Domingo‐Vidal

Whitaker‐Menezes

Martos-Rus

et al. 2019

Molecular Cancer Research

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Head and neck squamous cell carcinoma (HNSCC) is comprised of metabolically linked distinct compartments. Cancer-associated fibroblasts (CAF) and nonproliferative carcinoma cells display a glycolytic metabolism, while proliferative carcinoma cells rely on mitochondrial oxidative metabolism fueled by the catabolites provided by the adjacent CAFs. Metabolic coupling between these reprogrammed compartments contributes to HNSCC aggressiveness. In this study, we examined the effects of cigarette smoke–exposed CAFs on metabolic coupling and tumor aggressiveness of HNSCC. Cigarette smoke (CS) extract was generated by dissolving cigarette smoke in growth media. Fibroblasts were cultured in CS or control media. HNSCC cells were cocultured in vitro and coinjected in vivo with CS or control fibroblasts. We found that CS induced oxidative stress, glycolytic flux and MCT4 expression, and senescence in fibroblasts. MCT4 upregulation was critical for fibroblast viability under CS conditions. The effects of CS on fibroblasts were abrogated by antioxidant treatment. Coculture of carcinoma cells with CS fibroblasts induced metabolic coupling with upregulation of the marker of glycolysis MCT4 in fibroblasts and markers of mitochondrial metabolism MCT1 and TOMM20 in carcinoma cells. CS fibroblasts increased CCL2 expression and macrophage migration. Coculture with CS fibroblasts also increased two features of carcinoma cell aggressiveness: resistance to cell death and enhanced cell migration. Coinjection of carcinoma cells with CS fibroblasts generated larger tumors with reduced apoptosis than control coinjections, and upregulation of MCT4 by CS exposure was a driver of these effects. We demonstrate that a tumor microenvironment exposed to CS is sufficient to modulate metabolism and cancer aggressiveness in HNSCC. Implications: CS shifts cancer stroma toward glycolysis and induces head and neck cancer aggressiveness with a mitochondrial profile linked by catabolite transporters and oxidative stress. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/17/9/1893/F1.large.jpg.

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“…The polarisation of M1 and M2 macrophages are important for disease regulation. Previous studies have documented that activated macrophages are prominent in lung infection with bacteria [11] and viruses [12,13] as well as in lungs from smokers and chronic obstructive pulmonary disease (COPD) [14]. The main purpose of this study was to investigate the status of lung macrophages, as to M1/M2 subtypes in severe P. falciparum malaria patients with and without PE.…”

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confidence: 99%

M1 macrophage activation in severe Plasmodium falciparum malaria patients with pulmonary oedema

Klinkhamhom

Glaharn

Sris

et al. 2020

Preprint

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Background Pulmonary oedema (PE) is a serious complication of severe P. falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarisation is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarisation of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients with and without evidence of PE.Methods Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorised into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68-all macrophages, CD40-M1 macrophage and CD163-M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes. ResultsLung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE (p < 0.05), whereas there was no difference observed for CD163 (M2 macrophage) between PE and non-PE groups. ConclusionsThe study demonstrates M1 polarisation in lung tissues from severe P. falciparum malaria infections with PE. Understanding the nature of macrophage characterisation in malaria infection may provide new insights into therapeutic approaches that could be deployed to reduce lung damage in severe P. falciparum malaria. BackgroundPulmonary oedema (PE) is one of the major complications and therapeutic challenges in severe P. falciparum malaria. This condition is associated with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) [1]. The incidence of ARDS in severe P. falciparum patients ranges from 14%-26%, with the mortality rate of 14%-89% [2][3][4]. In addition, PE occurs in approximately 10%-21% [1,5, 6]. In P. falciparum malaria, PE is associated with inflammatory infiltrates consisting of mainly mononuclear cells, haemozoin deposit, the accumulation of macrophages, as well as parasite

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High infiltration of CD68+ macrophages is associated with poor prognoses of head and neck squamous cell carcinoma patients and is influenced by human papillomavirus

Cited by 60 publications

References 39 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

Cigarette Smoke Induces Metabolic Reprogramming of the Tumor Stroma in Head and Neck Squamous Cell Carcinoma

M1 macrophage activation in severe Plasmodium falciparum malaria patients with pulmonary oedema

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