Impacts of Ionizing Radiation on the Different Compartments of the Tumor Microenvironment

During the last decade, the initial cancer cell-centered view of tumors has greatly evolved to an integrated vision of tumor biology taking into account the key contribution of the TME.
Obviously, the different compartments of TME are closely related and contribute not only to tumor progression, but also to its response to treatments. Importantly, the TME evolves over
time during the different steps of cancer development and is also affected by different therapeutic modalities. Although, improvements have been achieved regarding RT delivery
to the primary tumor, ionizing radiation also target nontumor cells that influence tumor growth and metastatic dissemination. Different approaches have been proposed to
overcome the radioresistance of cancer cells. The TME-mediated radioresistance is now the object of researches, which has been elegantly reviewed recently by Barker et al. (2015) and severalarticles pointed out the importance of treatments that modify the TME and likely radiosensitize tumor (Ansiaux et al., 2005; Crokart et al., 2005b; Frérart et al., 2008).
However, the impact of anti-cancer treatments on the TME and consequently on the tumor phenotype, response to treatment and metastases, is often neglected. Here we
pointed out the impact of RT on the TME. Recent findings emphasize the interest to optimize RT (i.e., dose per fraction) and timing of surgery (Leroi et al., 2015; Surace et al.,
2015) in order to prevent metastatic spreading. The future challenge in RT will be to define the most appropriate combinations between RT, and other therapeutic modalities with the optimal sequence and timing of treatments. In this context, investigation of the TME-related acquired resistance will be essential and will provide important innovative data.