Radiotherapy, immunotherapy, and the tumour microenvironment: Turning an immunosuppressive milieu into a therapeutic opportunity

Immune checkpoint blockade (ICB) has revolutionised the treatment of solid tumours, yet most patients do not derive a clinical benefit. Resistance to ICB is often contingent on tumour microenvironment (TME) and modulating aspects this immunosuppressive milieu goal combination approaches. Radiation been used for over century in management cancer with more than half all receiving radiotherapy. Here, we outline rationale behind combining radiotherapy ICB, potential synergy through mutually beneficial remodelling TME. We discuss pleiotropic effects radiation TME including immunogenic cell death, activation cytosolic DNA sensors, stroma vasculature, paradoxical infiltration both anti-tumour suppressive immune populations. These events depend dose fractionation optimising these parameters will be key develop safe effective regimens. Finally, highlight ongoing efforts that combine radiation, immunotherapy inhibitors damage response, which can help achieve favourable equilibrium between tolerogenic microenvironment.