Didier Dequanter

Background: Head and neck cancer (HNC) is a complex affection. Nowadays, conventional treatments are associated with many side effects, reducing the patient’s quality of life. Recent studies suggest that metformin, a first-line treatment for diabetes, could decrease cancer incidence and improve cancer-related survival rates. Methods: This systematic review summarizes important data from studies evaluating metformin’s contribution to preventing and treating HNC. Results: The results suggest a protective effect of metformin in HNC. However, no consensus has been found on its therapeutic effects. Metformin seems to confer an improved cancer-related survival rate in a diabetic population, but compared to a non-diabetic population, the review could not identify any advantages. Nevertheless, no studies presented a negative impact. Conclusion: In conclusion, the results of this systematic review suggest that HNC patients may benefit from metformin. Indeed, it would reduce the HNC incidence. However, more studies are required to evaluate the effect on cancer-related survival rates.

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.