Search

Tumor-associated macrophages are key components of the tumor microenvironment (TME) and have been shown to play important roles in the progression of head and neck cancer. As a result, novel treatment approaches are focused on reprogramming M2 macrophages to adopt the M1 phenotype. A 3D coculture model was established to analyze the influence of cancer cells on monocyte recruitment and their polarization. Macrophages phenotypes were determined by immunofluorescence, western blot and RT-QPCR. Interleukines were analyzed by using CBA array. First, a scoring system based on the high or low density of M1 CD80+ and M2 CD163+ macrophages and on the tumor-infiltrated phenotype was developed in a clinical series of 54 head and neck squamous cell carcinoma patients. Interestingly, this macroscore was found to be more powerful than TNM criteria and p16 status and also significantly associated with poor prognosis for these patients. In vitro, the 3D model demonstrated that cancer cells are responsible for monocyte recruitment and M2 polarization, resulting in an immunosuppressive microenvironment with an increased production of IL8 and IL10 cytokines.Finally, we focused on a new compound found in toad venom. Bufalin is an endogenous cardiotonic steroid with reported anti-cancer and immunomodulatory properties. Our data indicated that bufalin reprogram M2 macrophages towards the M1 phenotype underlining its potential as an antitumor immune modulator. Overall, this research highlights the power of the macroscore as a new valuable prognostic biomarker and sheds light on the immunosuppressive tumor microenvironment. Moreover, it indicates that modulating macrophages in the tumor microenvironment using bufalin could be a promising immunotherapeutic strategy for the treatment of cancer. [ABSTRACT FROM AUTHOR]