Prostate cancer (PC) is frequently cured with high-dose rate brachytherapy (HDRBT) as a front-line treatment. However, a significant number develop intrinsic resistance. Immune responses are implicated in driving tumour-eradication, but PC is generally considered to be an immune-excluded tissue. Radiation is known to stimulate the immune system and overcome immune suppression in various cancers. Unfortunately, this has not yet been proven in PC, yet is used as the rationale for numerous clinical trials combining radiation and immunotherapies. We hypothesise that radiation overcomes the immunosuppressive nature of PC in a predictable way - providing rationale for immunomodulators in conjunction with radiation. Our primary goal is comprehensively describing the response of prostate tissue to radiation.
We present here the results of comprehensive immunoprofiling of a cohort of world-unique paired pre- and post-radiation tissues from 24 PC patients (RadBank cohort). The data includes multiplex IHC of 14 distinct cell subsets, uropathological tissue segmentation (tumour/non-tumour), gene signature profiling, digital spatial profiling, T-cell receptor sequencing, and immune cell spatial analysis.
Our data resolved distinct classes of tissue and subsequent radiation responses, based on demonstrably radiosensitive immune cell types (Tregs, macrophages and dendritic cells), as well as gene signatures (tumour inflammation score : TIS) of suppressed immune activation. Interestingly, these changes are largely agnostic of tumor content. Spatial interaction remodelling, T cell clone sequencing, and various clinical variables (e.g. Gleason grade, Androgen deprivation) could all influence immunomodulation following HDRBT.
This study provides original insights into the radioimmunobiology of the prostate and provides first-in-human data to guide the development of novel combinatorial therapies that improve outcomes for localised PC.