Predicting radiation-induced immune trafficking and activation in localized prostate cancer.

Abstract

340 Background: Prostate cancer is frequently cured with high-dose rate brachytherapy as a front-line treatment. However, a significant number unfortunately develop intrinsic resistance. Although considered to be an immune-excluded tissue, immune responses are implicated in driving tumour-eradication in prostate cancer. This has not been proven, and yet is used as the rationale for numerous clinical trials combining radiation and immunotherapies. We hypothesise that there is a predictable but differential relationship between radiation and the immune responses in prostate cancer that could be used to fulfil a clinical need - identifying patients that would benefit from immune intervention in conjunction with radiation. Methods: We present here the results of comprehensive immunological profiling of a cohort of world-unique pre- and post-radiation tissues from 24 patients (RadBank cohort). These were assessed using pathological classification, tissue segmentation (cancer/surrounding stroma), multiplex IHC, gene expression profiling, T-cell receptor sequencing, and spatial computational analysis. Results: Our data resolved three classes of prostate cancer tissue based on immune infiltrate level, immune-activation and -checkpoint gene signatures, spatial clustering and T cell clone sequencing: We have begun to resolve clear patient and clinical classifiers based on immune responses to radiation, and identified patients groups likely to benefit from immune therapy alongside radiation. Conclusions: Importantly, these classifications are associated with baseline gene expression profiles that may be used for pre-clinical stratification and more sophisticated treatment paradigms.