Radiation, inflammation and the immune response in cancer

Abstract

Radiation is an important component of cancer treatment with more than half of all patients receive radiotherapy during their cancer experience. While the impact of radiation on tumour morphology is routinely examined in the pre-clinical and clinical setting, the impact of radiation on the tumour microenvironment and more specifically the inflammatory/immune response is less well characterised. Inflammation is a key contributor to short- and long-term cancer eradication, with significant tumour and normal tissue consequences. Therefore, the role of radiation in modulating the inflammatory response is highly topical given the current wave of targeted and immuno-therapeutic treatments for cancer. This review provides a general overview of how radiation modulates the inflammatory and immune response-(i) how radiation induces the inflammatory/immune system, (ii) the cellular changes that take place, (iii) how radiation dose delivery affects the immune response, and (iv) a discussion on research directions to improve patient survival, reduce side effects, improve quality of life, and reduce financial costs in the immediate future. Harnessing the benefits of radiation on the immune response will enhance its maximal therapeutic benefit and reduce radiation-induced toxicity.

Fig. 1

Radiation-induced factors that initiate and modulate the inflammatory/immune response

Fig. 2

Schematic overview of the interconnected network of inflammatory and immune response pathways activated by IR. Zones represent the topics discussed in this review; (1) cytokines, growth factors, adhesion molecules (“Cytokines, chemokines, growth factors, adhesion molecules and coagulation factors” section), (2) DNA damage, ER stress, ROS/RNS, hypoxia (“DNA damage, reactive oxygen/nitrogen species, ER stress, and hypoxia” section), (3) inflammasomes (“Inflammasomes”), (4) cell death and senescence (“Cell death and senescence” section), and (5) coagulation and fibrinolysis (“Cytokines, chemokines, growth factors, adhesion molecules and coagulation factors” section). Straight arrows denote activation. Two-headed arrows denote bidirectional activation. Curved arrows denote a catalytic or enzymatic action. Figure prepared using Servier Medical Art (https://smart.servier.com/)

Fig. 3

Role of the innate and adaptive immune cells following the irradiation of tumour cells. HPC haematopoietic progenitor cells. Bold text and arrows denote the essential pathway of RT-induced immune activation by (i) direct or indirect (ROS-RNS-mediated) DNA damage, (ii) antigen presentation and activation by DCs, and (iii) expansion and specificity of the adaptive immune response. Image modified from (Kamrava et al. 2009) and prepared using Servier Medical Art (https://smart.servier.com/)

Fig. 4

Aspects of radiation delivery that modulate the inflammatory/immune response