Dealing with Macrophage Plasticity to Address Therapeutic Challenges in Head and Neck Cancers

Furgiuele, Sonia; Descamps, Géraldine; Cascarano, Lorena; Boucq, Ambre; Dubois, Christine; Journé, Fabrice; Saussez, Sven

doi:10.3390/ijms23126385

Cited by 9 publications

(6 citation statements)

References 70 publications

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“…S5F), suggesting that KCs might be activated by GLY to maintain the immunological homeostasis. It has been reported that the expression of CD68 (a macrophage marker) was enhanced after macrophage activation [49], and the increased CD68 expression after GLY treatment was also observed in our work (Fig. 4H).…”

Section: Gene Expression Heterogeneity Of Kcs In Gly-treated Mouse Li...supporting

confidence: 89%

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice

Sun

Hong

et al. 2023

Cell Mol Biol Lett

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Background Glyphosate (GLY), as the active ingredient of the most widely used herbicide worldwide, is commonly detected in the environment and living organisms, including humans. Its toxicity and carcinogenicity in mammals remain controversial. Several studies have demonstrated the hepatotoxicity of GLY; however, the underlying cellular and molecular mechanisms are still largely unknown. Methods Using single-cell RNA sequencing (scRNA-seq), immunofluorescent staining, and in vivo animal studies, we analyzed the liver tissues from untreated and GLY-treated mice. Results We generated the first scRNA-seq atlas of GLY-exposed mouse liver. GLY induced varied cell composition, shared or cell-type-specific transcriptional alterations, and dysregulated cell–cell communication and thus exerted hepatotoxicity effects. The oxidative stress and inflammatory response were commonly upregulated in several cell types. We also observed activation and upregulated phagocytosis in macrophages, as well as proliferation and extracellular matrix overproduction in hepatic stellate cells. Conclusions Our study provides a comprehensive single-cell transcriptional picture of the toxic effect of GLY in the liver, which offers novel insights into the molecular mechanisms of the GLY-associated hepatotoxicity.

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Section: Gene Expression Heterogeneity Of Kcs In Gly-treated Mouse Li...supporting

confidence: 89%

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice

Sun

Hong

et al. 2023

Cell Mol Biol Lett

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“…All 73 FFPE specimens were labeled by immunohistochemistry for CD163 and CD80 immune markers to identify M2 and M1 macrophage populations, respectively. The protocol was fully described in a previous publication [ 52 ]. To determine the transcriptional status of HPV, all specimens were further immunohistochemically evaluated for p16 expression using a mouse monoclonal antibody (CINtec p16, Ventana, Tucson, AZ, USA) and an automated immunostainer at the Jules Bordet Institute (Bond-Max, Leica Microsystems, Wetzlar, Germany), as described previously [ 53 ].…”

Section: Methodsmentioning

confidence: 99%

Macrophage Profiling in Head and Neck Cancer to Improve Patient Prognosis and Assessment of Cancer Cell–Macrophage Interactions Using Three-Dimensional Coculture Models

Mhaidly

Journé

Najem

et al. 2023

IJMS

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Tumor-associated macrophages are key components of the tumor microenvironment and play important roles in the progression of head and neck cancer, leading to the development of effective strategies targeting immune cells in tumors. Our study demonstrated the prognostic potential of a new scoring system (Macroscore) based on the combination of the ratio and the sum of the high and low densities of M1 (CD80+) and M2 (CD163+) macrophages in a series of head and neck cancer patients, including a training population (n = 54) and a validation population (n = 19). Interestingly, the Macroscore outperformed TNM criteria and p16 status, showing a significant association with poor patient prognosis, and demonstrated significant predictive value for overall survival. Additionally, 3D coculture spheroids were established to analyze the crosstalk between cancer cells and monocytes/macrophages. Our data revealed that cancer cells can induce monocyte differentiation into protumoral M2 macrophages, creating an immunosuppressive microenvironment. This coculture also induced the production of immunosuppressive cytokines, such as IL10 and IL8, known to promote M2 polarization. Finally, we validated the ability of the macrophage subpopulations to induce apoptosis (M1) or support proliferation (M2) of cancer cells. Overall, our research highlights the potential of the Macroscore as a valuable prognostic biomarker to enhance the clinical management of patients and underscores the relevance of a spheroid model in gaining a better understanding of the mechanisms underlying cancer cell–macrophage interactions.

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“…In general, macrophages associated with tumors play an important role in both the immune system and tumor microenvironment, and interact with different pathways, including ferroptosis, which are involved in cancer initiation, proliferation, metastasis, in drug resistance, etc. [ 81 , 162 , 163 , 164 , 165 , 166 ]. In particular, during cancer proliferation, adjacent endothelial and other cells are utilized by cancer cells for energy supply and nutrients, including iron, most of which is released during ferritinophagy.…”

Section: Excess Iron Deposition and Toxicity In Non-transfusional Iro...mentioning

confidence: 99%

Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications

Kontoghiorghes

2023

IJMS

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Iron is essential for all organisms and cells. Diseases of iron imbalance affect billions of patients, including those with iron overload and other forms of iron toxicity. Excess iron load is an adverse prognostic factor for all diseases and can cause serious organ damage and fatalities following chronic red blood cell transfusions in patients of many conditions, including hemoglobinopathies, myelodyspasia, and hematopoietic stem cell transplantation. Similar toxicity of excess body iron load but at a slower rate of disease progression is found in idiopathic haemochromatosis patients. Excess iron deposition in different regions of the brain with suspected toxicity has been identified by MRI T2* and similar methods in many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Based on its role as the major biological catalyst of free radical reactions and the Fenton reaction, iron has also been implicated in all diseases associated with free radical pathology and tissue damage. Furthermore, the recent discovery of ferroptosis, which is a cell death program based on free radical generation by iron and cell membrane lipid oxidation, sparked thousands of investigations and the association of iron with cardiac, kidney, liver, and many other diseases, including cancer and infections. The toxicity implications of iron in a labile, non-protein bound form and its complexes with dietary molecules such as vitamin C and drugs such as doxorubicin and other xenobiotic molecules in relation to carcinogenesis and other forms of toxicity are also discussed. In each case and form of iron toxicity, the mechanistic insights, diagnostic criteria, and molecular interactions are essential for the design of new and effective therapeutic interventions and of future targeted therapeutic strategies. In particular, this approach has been successful for the treatment of most iron loading conditions and especially for the transition of thalassemia from a fatal to a chronic disease due to new therapeutic protocols resulting in the complete elimination of iron overload and of iron toxicity.

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Dealing with Macrophage Plasticity to Address Therapeutic Challenges in Head and Neck Cancers

Cited by 9 publications

References 70 publications

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice

Macrophage Profiling in Head and Neck Cancer to Improve Patient Prognosis and Assessment of Cancer Cell–Macrophage Interactions Using Three-Dimensional Coculture Models

Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications

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