ReviewStereotactic ablative body radiotherapy combined with immunotherapy: Present status and future perspectivesAssociation de radiothérapie stéréotaxique ablative et d’immunothérapie : présent et avenir
Section snippets
Stereotactic ablative body radiotherapy
Stereotactic ablative body radiotherapy is a form of high-precision radiotherapy delivering extremely high ablative doses of radiation, usually in three to eight fractions, combining reproducible patient immobilization, tumour motion tracking and steep dose gradients, resulting in reduced normal tissue toxicity [1]. Stereotactic ablative body radiotherapy achieves excellent local control rates in patients with stage I/II non-small cell lung cancer and liver metastases of colorectal cancer [2].
Tumorigenesis and the immune system
The immune system closely monitors the process of tumorigenesis first by registering the presence of cells undergoing neoplastic transformation, and second by interacting with neoplastic cells to mediate their destruction. Solid tumours have developed mechanisms to escape “cancer immunosurveillance”, i.e., detection by the immune system. This is achieved by, among other mechanisms, the secretion of potent immune-suppressive cytokines and the expression of T cell inhibitory molecules, which are
Breaking the immune tolerance using checkpoint modulators
Immune-checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system. These are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues, in order to minimize collateral tissue damage. It is now clear that tumours use certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against tumour antigen specific T cells. Examples of these immune-checkpoints are
Preclinical results
Several studies have focused on the immunogenic response of tumours to different dose schedules of radiotherapy. Lee et al. observed that a single dose of ablative radiotherapy (20 Gy) generated a CD8+ T cell-dependent immunity leading to tumour reduction and eradication of metastasis [37]. In comparison, mice treated with 4 × 5 Gy initially responded to radiotherapy but tumours relapsed over time. One possible explanation is that fractionated low-dose radiotherapy may kill infiltrating CD8+ T
Conclusion
In conclusion, these data show that immunogenic cell death caused by different strategies of radiotherapy can be used in combination with immunotherapy to induce a CD8+ T cell mediated anti-tumour response, which leads to tumour control of the irradiated tumour and often to tumour control outside the radiation field, i.e., an abscopal effect in different preclinical models. However, there is not yet a uniform combination strategy for the best radiotherapy schedule/dose and immunotherapeutic
Disclosure of interest
The authors declare that they have no conflicts of interest concerning this article.
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