Abstract 686P
Background
The advent of rapid sequencing technologies permits novel targeting of immunotherapy treatment modalities for prostate cancer, as increasing evidence shows that standard clinicopathological factors are not accurate prognosticators for newly diagnosed disease. This study leverages clinical and genomic data from The Cancer Genome Atlas (TCGA) to characterize tumor immune microenvironment (TIME) in a cohort of prostate adenocarcinoma (PRAD) patients and assess relationships between TIME composition, progression-free survival (PFS) and response to radiation therapy.
Methods
Tumors were clustered based on the immune profiles of their tumors using CIBERSORTX, and differential gene expression analysis was performed on each cluster using DE Analysis App (Shiny). Differentially expressed genes were correlated to their role in cancer hallmarks through query of misigdb hallmarks library and input into multivariate analysis. Clinical data was obtained from Broad Institute’s Firebrowse tool; survival analyses were performed using Kaplan-Meier estimates and the log-rank test.
Results
496 patients were divided into 4 clusters. The two macrophage-predominant subgroups demonstrated significantly decreased PFS compared to the macrophage-depleted clusters (HR 2.442, 95% CI 1.712 – 3.482, p < 0.0001). Within the macrophage-predominant clusters, the radiated M0-predominant cluster demonstrated decreased PFS compared to the radiated M2-predominant cluster (HR 1.93, 95% CI 1.081 – 3.446, p = 0.025).
Conclusions
A predominance of macrophages, most notably M0 macrophages, may confer poorer prognosis in patients with PCa, especially those undergoing radiation. Macrophage-depletion therapies may be considered to improve response to radiation in macrophage-predominant subgroups, and especially in M0 macrophage-predominant PCa. Additionally, this analysis supports the need for further research into targeted immunotherapy and immunoradiotherapy treatments for patients with PCa.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
NIH, Prostate Cancer Foundation.
Disclosure
D.E. Spratt: Research grant/Funding (self): Janssen; Non-remunerated activity/ies: Blue Earth; Non-remunerated activity/ies: AstraZeneca. All other authors have declared no conflicts of interest.