Radiation, Inflammation, and Immune Responses in Cancer

Gabriele Multhoff,Jürgen Radons

doi:10.3389/fonc.2012.00058

Abstract

Chronic inflammation has emerged as one of the hallmarks of cancer. Inflammation also plays a pivotal role in modulating radiation responsiveness of tumors. As discussed in this review, ionizing radiation (IR) leads to activation of several transcription factors modulating the expression of numerous mediators in tumor cells and cells of the microenvironment promoting cancer development. Novel therapeutic approaches thus aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts. Among them, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. A great variety of classical or novel drugs including nutraceuticals such as plant phytochemicals have the capacity to interfere with the inflammatory network in cancer and are considered as putative radiosensitizers. Thus, targeting the inflammatory signaling pathways induced by IR offers the opportunity to improve the clinical outcome of radiation therapy by enhancing radiosensitivity and decreasing putative metabolic effects. Since inflammation and sex steroids also impact tumorigenesis, a therapeutic approach targeting glucocorticoid receptors and radiation-induced production of tumorigenic factors might be effective in sensitizing certain tumors to IR.

Highlights

Chronic inflammation has emerged as one of the hallmarks of cancer impacting any stage of tumorigenesis (Colotta et al, 2009; Grivennikov and Karin, 2010)
Novel therapeutic approaches aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts
INFLAMMATION AND RADIATION Several lines of evidence indicate that inflammation plays a pivotal role in modulating radiation responsiveness of tumors

Summary

INTRODUCTION

Chronic inflammation has emerged as one of the hallmarks of cancer impacting any stage of tumorigenesis (Colotta et al, 2009; Grivennikov and Karin, 2010). The tumor cell-derived pro-inflammatory molecules activate the same transcription factors within the cells of the microenvironment and the tumor cells themselves resulting in a more pronounced generation of inflammatory mediators driving a tumor-promoting amplification loop. This amplification mechanism further enhances the impact of inflammatory stimuli within the tumor environment and triggers the manifestation of a cancer-related inflammatory milieu contributing to tumor growth and invasiveness. Targeting the proinflammatory signaling pathways for tumor radiosensitization represents a promising novel therapeutical approach in cancer. Interrupting the inflammatory network in cancer by targeting these molecules may be a promising radiosensitization approach in cancer therapy.

Radiation and inflammation in cancer

TRAIL Treg cells