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Tumor microenvironment and radioresistance

Tatsuya Suwa,Minoru Kobayashi,Jin-Min Nam,H. Harada

Published 2021 in Experimental and Molecular Medicine

ABSTRACT

Metastasis is not the result of a random event, as cancer cells can sustain and proliferate actively only in a suitable tissue microenvironment and then form metastases. Since Dr. Stephen Paget in the United Kingdom proposed the seed and soil hypothesis of cancer metastasis based on the analogy that plant seeds germinate and grow only in appropriate soil, considerable attention has focused on both extracellular environmental factors that affect the growth of cancer cells and the tissue structure that influences the microenvironment. Malignant tumor tissues consist of not only cancer cells but also a wide variety of other cells responsible for the inflammatory response, formation of blood vessels, immune response, and support of the tumor tissue architecture, forming a complex cellular society. It is also known that the amounts of oxygen and nutrients supplied to each cell differ depending on the distance from tumor blood vessels in tumor tissue. Here, we provide an overview of the tumor microenvironment and characteristics of tumor tissues, both of which affect the malignant phenotypes and radioresistance of cancer cells, focusing on the following keywords: diversity of oxygen and nutrient microenvironment in tumor tissue, inflammation, immunity, and tumor vasculature. Extensive research into diverse tumor microenvironments in all cancer types is needed to inform novel therapeutic strategies. For cancer to metastasize, the conditions of the surrounding tumor microenvironment must be just right; this ‘seed and soil’ hypothesis has prompted recent research into extracellular factors influencing cancer behavior. Hiroshi Harada at Kyoto University in Japan and co-workers reviewed current understanding of tumor microenvironments and their influence on radiation resistance. Every tumor displays a unique microenvironment comprising multiple cell types involved in complex crosstalk, and the composition of these cellular communities influences inflammation, blood vessel formation and immune responses. On acute and chronic timescales, the levels of oxygen and nutrients reaching cancer cells varies widely across tumor regions, dynamically influencing character of cancer cells. The presence of diverse cellular society and oxygen-poor tumor regions eventually appear to reduce radiotherapy success.

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