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

Mhaidly, Nour; Journé, Fabrice; Najem, Ahmad; Stock, Lawrence M.; Trelcat, Anne; Dequanter, Didier; Saussez, Sven; Descamps, Géraldine

doi:10.3390/ijms241612813

Cited by 2 publications

(1 citation statement)

References 53 publications

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“…The worldwide incidence of Head & Neck Squamous Cell Carcinoma (HNSCC) was estimated at 900,000 new cases and 467,000 deaths in 2020, making it the seventh most common malignant tumor in the world. 1 Despite advances in the treatment and understanding of disease biology, the prognosis of patients with HNSCC remains uncertain. One of the major causes of therapy failure is the heterogeneity of the tumor microenvironment (TME), which creates hypoxic and acidic regions, thus affecting sensitivity to anti-cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

A Macrophages-Enriched Head and Neck Tumor Spheroid Model to Study Foslip® Behavior in Tumor Microenvironment

Francois,

Dirheimer,

Chateau

et al. 2023

IJN

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Purpose The tumor microenvironment (TME) is composed of various stromal components, including immune cells such as tumor-associated macrophages (TAMs), which play a crucial role in cancer initiation and progression. TAMs can exhibit either a tumor-suppressive M1 or a tumor-promoting M2 phenotype. First, we aimed to develop a 3D human heterotypic model consisting of head and neck squamous cell carcinoma (HNSCC) cells and different subtypes of macrophages to replicate the interactions between immune cells and cancer cells. We further investigated the behavior of Foslip ® , a liposomal formulation of temoporfin, using a macrophage-enriched 3D model. Methods Monocytes were differentiated into M1 and M2 macrophages, which represent two distinct subtypes. Following histological and molecular characterization, these macrophages were used to establish a 3D spheroid model of HNSCC enriched with either polarized macrophages or conditioned media. Flow cytometry and fluorescence microscopy were used to assess the accumulation and distribution of Foslip ® . The cytotoxic effect of Foslip ® -mediated photodynamic therapy (PDT) was evaluated using flow cytometry. Results We developed heterotypic spheroids characterized by a mixed phenotype of evenly distributed macrophages. In this 3D co-culture model, both M1 and M2 macrophages showed significantly higher accumulation of Foslip ® compared to the cancer cells. Although this differential accumulation did not drastically affect the overall PDT efficiency, spheroids generated with conditioned media exhibited a significant enhancement in photo-induced cell death, suggesting that the microenvironment could modulate the response to Foslip ® -PDT. Conclusion 3D models of HNSCC cells and macrophages provide valuable insights into the complex response of HNSCC cells to PDT using Foslip ® in vitro. This model can be used to screen immunomodulatory nanomedicines targeting TAMs in solid head and neck tumors, either alone or in combination with standard therapies.

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Section: Introductionmentioning

confidence: 99%

A Macrophages-Enriched Head and Neck Tumor Spheroid Model to Study Foslip® Behavior in Tumor Microenvironment

Francois,

Dirheimer,

Chateau

et al. 2023

IJN

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Bufalin Suppresses Head and Neck Cancer Development by Modulating Immune Responses and Targeting the β-Catenin Signaling Pathway

Mhaidly,

Barake,

Trelcat

et al. 2024

Cancers

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Bufalin, a cardiotonic steroid derived from the Chinese toad (Bufo gargarizans), has demonstrated potent anticancer properties across various cancer types, positioning it as a promising therapeutic candidate. However, comprehensive mechanistic studies specific to head and neck cancers have been lacking. Our study aimed to bridge this gap by investigating bufalin’s mechanisms of action in head and neck cancer cells. Using several methods, such as Western blotting, immunofluorescence, and flow cytometry, we observed bufalin’s dose-dependent reduction in cell viability, disruption of cell membrane integrity, and inhibition of colony formation in both HPV-positive and HPV-negative cell lines. Bufalin induces apoptosis through the modulation of apoptosis-related proteins, mitochondrial function, and reactive oxygen species production. It also arrests the cell cycle at the G2/M phase and attenuates cell migration while affecting epithelial–mesenchymal transition markers and targeting pivotal signaling pathways, including Wnt/β-catenin, EGFR, and NF-κB. Additionally, bufalin exerted immunomodulatory effects by polarizing macrophages toward the M1 phenotype, bolstering antitumor immune responses. These findings underscore bufalin’s potential as a multifaceted therapeutic agent against head and neck cancers, targeting essential pathways involved in proliferation, apoptosis, cell cycle regulation, metastasis, and immune modulation. Further research is warranted to validate these mechanisms and optimize bufalin’s clinical application.

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

Cited by 2 publications

References 53 publications

A Macrophages-Enriched Head and Neck Tumor Spheroid Model to Study Foslip® Behavior in Tumor Microenvironment

A Macrophages-Enriched Head and Neck Tumor Spheroid Model to Study Foslip® Behavior in Tumor Microenvironment

Bufalin Suppresses Head and Neck Cancer Development by Modulating Immune Responses and Targeting the β-Catenin Signaling Pathway

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