Hypoxia-driven immunosuppression: A new reason to use thermal therapy in the treatment of cancer?

Abstract

Hypoxia within the tumour microenvironment is correlated with poor treatment outcome after radiation and chemotherapy, and with decreased overall survival in cancer patients. Several molecular mechanisms by which hypoxia supports tumour growth and interferes with effective radiation and chemotherapies are now well established. However, several new lines of investigation are pointing to yet another ominous outcome of hypoxia in the tumour microenvironment: suppression of anti-tumour immune effector cells and enhancement of tumour escape from immune surveillance. This review summarises this important information, and highlights mechanistic data by which hypoxia incapacitates several different types of immune effector cells, enhances the activity of immunosuppressive cells and provides new avenues which help ‘blind’ immune cells to detect the presence of tumour cells. Finally, we discuss data which indicates that mild thermal therapy, through its physiologically regulated ability to alter vascular perfusion and oxygen tensions within the tumour microenvironment, as well as its ability to enhance the function of some of the same immune effector activities that are inhibited by hypoxia, could be used to rapidly and safely release the tight grip of hypoxia in the tumour microenvironment thereby reducing barriers to more effective immune-based therapies.

• hypoxia, anti-tumour immunity
• thermoregulation
• hyperthermia
• tumour microenvironment

Acknowledgements

Dr. Lee and Dr. Mace contributed equally to this manuscript. This work was supported by grants NIH R01 CA135368-01A1, R01 CA071599-11, 2 T32 CA085183 Immunology Department Training Grant, and the Roswell Park Cancer Institute Core grant CA16056. The authors would like to thank Drs Melissa Grimm and Bonnie Hylander for their helpful comments on the manuscript.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the context and writing of the article.