RadPath: a pathology network to investigate the immune effects of radiotherapy

Background: Immuno-oncology (IO) agents are revolutionizing the treatment of cancer, but the underlying mechanisms that are responsible for success or failure, including when combining immune checkpoint blockade with radiotherapy (RT), remain poorly understood.

Hence, whilst some clinical success has been seen with RT/IO combinations, the biology of the immune response to RT in patients, in standard of care RT treatments as well as in the context of RT/IO trial combinations, needs in depth investigation to inform future clinical direction and trial strategy.

An under-investigated area of immune analysis of patient samples is pathology, despite the potential of new developments in digitalisation, AI and multicolour immunofluorescence (mIF) to quantify different immune cell subsets.

Pathological readouts of the tumour immune microenvironment (TIME), how it changes with RT, and how it links to other analyses (eg genomic), as well as clinical outcome, can improve both our basic scientific understanding of the immunology of RT, and hence the design of trials to improve patient outcomes.

This proposal has developed from the RadNet Immunology Working Group and focuses on providing immune pathology support across the RadNet network.

Aims: We will establish a co-ordinated immune pathology network (RadPath) across RadNet, led by the Institute of Cancer Research, Manchester and Leeds, with the active participation and support from all other centres.

This infrastructure will allow samples collected from patients taking part in academic or industry-sponsored trials including RT as a treatment modality, to be analysed for their TIME and, where available, normal tissue. The focus will be on fixed tissue to maximise deliverability, efficiency and affordability.

Methods: RadPath will first establish shared standard operating procedures, material transfer agreements and data sharing platforms, building on published collaborative work between RadNet centres.

Prioritising initially available samples and those expected within 2-years from ongoing studies, going forward RadPath will also regularly invite potential project proposals.

By requiring further academic and/or industrial funding beyond initial set-up, RadPath will develop longer-term sustainability. How the results of this research will be used: The results generated by RadPath will be shared across the network.

This will build a network of translational immune pathology science to inform better understanding of the interactions between RT and the immune system, and hence better design of treatment strategies including RT, to improve patient outcome.