Immunological aspects of radiotherapy.

Heike Scheithauer,Udo S Gaipl,Kirsten Lauber,Claus Belka

doi:10.1186/1748-717x-9-185

Abstract

The major objective of radiotherapy (RT) in the context of cancer treatment is the achievement of local tumor control. Traditionally, this is considered to be mediated by the induction of DNA damage, resulting in tumor cell death and abrogated clonogenic survival [1]. However, it has become more and more evident that distinct irradiation regimes as well as selected doses of ionizing radiation, and particularly the combination with immunotherapeutic approaches can induce or modulate systemic immune responses, which contribute to tumor control or inflammatory side effects, respectively. Locally administered RT can instigate systemic, abscopal, or 'out-of-field' effects, and meanwhile it is well acknowledged that DNA damage responses and immunological events, including anti-tumor immune mechanisms and inflammatory reactions are interconnected. The Special Topic Immunological aspects of radiotherapy aims to introduce radiation oncologists and researchers in the field of molecular and cellular oncology to the manifold aspects of how RT impacts on immune modulation, and how the combination with targeted therapies and selected immunotherapeutic strategies can result in improved local and systemic tumor control via the stimulation of anti-tumor immune responses. Focus is set on the immunological effects of different irradiation regimes and doses, synergistic effects between RT and immunotherapy with natural killer cells or mRNA-based vaccines, and finally on immunological normal tissue reactions.

Highlights

The major objective of radiotherapy (RT) in the context of cancer treatment is the achievement of local tumor control
Using glioblastoma cell lines with different p53 and O6-methylguanine DNA methyltransferase (MGMT) expression status, the authors examine the induction of glioblastoma cell death upon fractionated RT at daily doses of 2 Gy alone or in combination with clinically relevant concentrations of temozolomide (TMZ) and/or the histone deacetylase (HDAC) inhibitor valproic acid (VPA)
The authors conclude that especially in p53 mutant, MGMT positive glioblastoma fractionated RT and not chemotherapy with TMZ or VPA governs cell death induction and release of danger signals. Both might be relevant for shaping an immunogenic tumor microenvironment necessary for the induction of systemic anti-tumor immunity, and future research has to focus on how RT might contribute to the success of multimodal immunotherapeutic approaches for glioblastoma multiforme [7]

Summary

Introduction

The major objective of radiotherapy (RT) in the context of cancer treatment is the achievement of local tumor control. The authors characterize the type and the extent of cell death induced by fractionated and ablative radiotherapeutic regimes as well as the impact on the release of danger signals and monocyte attraction factors by dying breast cancer cells.

Results

Conclusion