Unravelling the effects of proton irradiation on macrophages in cancer
Promoter
Prof. Carine MICHIELS, UNamur, Laboratory of Cellular and Molecular Biology (URBC), Tumor Hypoxia (TumHyp) group
Jury
Olivier FERON (UCL), Peter HUBER (DKFZ, Heidelberg), Anne-Catherine HEUSKIN, présidente (UNamur), Yves POUMAY (UNamur), Stéphane LUCAS (UNamur), Carine MICHIELS, promoteur (UNamur)
Summary
Tumor-associated macrophages (TAMs) are the most abundant constituents of the tumor microenvironment. In addition, these cells influence key processes in tumor progression. TAMs are mostly associated to a M2-like phenotype, characterized by anti-inflammatory properties and pro-tumoral functions. This phenotype contrasts with the M1 phenotype which is associated to pro-inflammatory, phagocytic and anti-tumoral roles. Interestingly, microenvironmental changes in tumor may easily switch the phenotype from M2 to M1, or inversely. Therefore, re-educating M2-like TAMs towards a M1-like phenotype with treatment modalities represents a promising therapeutic strategy to elicit tumor regression. As a local treatment, radiotherapy represents an attractive strategy. Until now, conventional radiotherapy (X-rays and g-rays) have not succeeded in TAM reprogramming. As radiotherapy is a continuously evolving field, new types of advanced radiotherapy have emerged, such as protontherapy. By presenting several physical advantages over conventional radiotherapy, protontherapy is a powerful therapeutic tool used to precisely target the tumor. Interestingly, protontherapy has demonstrated different radiobiological effects on tumors compared to X-ray irradiation. Therefore, understanding the effects of proton irradiation on macrophages, and more specifically on their reprogramming, could allow re-evaluating the use of protontherapy for cancer treatment. For the first time, our study revealed that proton irradiation orchestrates macrophage reprogramming in M2-like macrophages through the activation of NFkB. Our results also evidenced that the presence of cancer cells does not influence proton-induced macrophage reprogramming. As a whole, this study further underpins the huge potential of protontherapy for targeting TAMs in tumors.