Targeting the Tumor Microenvironment in Radiation Oncology: Proceedings from the 2018 ASTRO-AACR Research Workshop.
McGee HM., Jiang D., Soto-Pantoja DR., Nevler A., Giaccia AJ., Woodward WA.
The development of cancers and their response to radiation are intricately linked to the tumor microenvironment in which they reside. Tumor cells, immune cells, and stromal cells interact with each other and are influenced by the microbiome and metabolic state of the host, and these interactions are constantly evolving. Stromal cells not only secrete extracellular matrix and participate in wound contraction, but they also secrete fibroblast growth factors (FGFs), which mediate macrophage differentiation. Tumor associated macrophages (TAMs) migrate to hypoxic areas and secrete VEGF to promote angiogenesis. The microbiome and its byproducts alter the metabolic milieu by shifting the balance between glucose utilization and fatty acid oxidation, and these changes subsequently influence the immune response in the tumor microenvironment (TME). Not only does radiation exert cell autonomous effects on tumor cells, but it influences both the tumor-promoting and tumor-suppressive components of the TME. To gain a deeper understanding of how the tumor microenvironment influences the response to radiation, the American Society for Radiation Oncology (ASTRO) and the American Association of Cancer Research (AACR) organized a scientific workshop on July 26-27, 2018, which focused on how the microbiome, the immune response, the metabolome, and the stroma all can shift the balance between radiosensitivity and radioresistance. The proceedings from this workshop are discussed here and highlight recent discoveries in the field as well as the most important areas for future research.