Enhancing the Bystander and Abscopal Effects to Improve Radiotherapy Outcomes

In this paper, we summarize published articles and experiences related to the attempt to improve radiotherapy outcomes and, thus, to personalize the radiation treatment according to the individual characteristics of each patient. The evolution of ideas and the study of successively published data have led us to envisage new biophysical models for the interpretation of tumor and healthy normal tissue response to radiation. In the development of the model, we have shown that when mesenchymal stem cells (MSCs) and radiotherapy are administered simultaneously in experimental radiotherapy on xenotumors implanted in a murine model, the results of the treatment show the existence of a synergic mechanism that is able to enhance the local and systemic actions of the radiation both on the treated tumor and on its possible metastasis. We are convinced that, due to the physical hallmarks that characterize the neoplastic tissues, the physical-chemical tropism of MSCs, and the widespread functions of macromolecules, proteins, and exosomes released from activated MSCs, the combination of radiotherapy plus MSCs used intratumorally has the effect of counteracting the pro-tumorigenic and pro-metastatic signals that contribute to the growth, spread, and resistance of the tumor cells. Therefore, we have concluded that MSCs are appropriate for therapeutic use in a clinical trial for rectal cancer combined with radiotherapy, which we are going to start in the near future.
This work was supported by the Spanish Ministry of Economy and Competitiveness, MINECO: SAF201240011-C02-02 and SAF2015-70520-R to JR; CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico—Brasil to VF; project of Excellence from the Andalusian Regional Government P12CTS-383 to FO; and the Spanish Ministry of Economy and Competitiveness SAF2012-40011-C02-01, SAF2015- 70520-R, RTICC RD12/0036/0026, and CIBER Cáncer ISCIII CB16/12/00421 to FO, VF, and JR.