Abstract
Abstract Background: The combination of radiation therapy and immunotherapy has emerged as an exciting field of research with the potential for significant clinical benefit. Using pre-treatment prostate biopsies from two clinical trials we explored the hypothesis that a validated gene expression signature of postoperative radiation therapy outcome score (PORTOS) is associated with differences in tumor molecular immunophenotype. In this study, we compared prostate tumors with high vs average PORTOS scores for expression of 32 molecular immunophenoscores that reflect cancer antigen profiles and the cellular composition of tumor infiltrating lymphocytes. Methods: Gene expression profiles were obtained from microdissected tumor tissue from 242 treatment naïve-prostate biopsy cores obtained from 92 patients enrolled in the University of Miami MAST (NCT02242773) and BLaStM (NCT02307058) clinical trials. For each biopsy the PORTOS score (PMID: 27743920) and 32 tumor molecular immunophenoscores (PMID: 28052254) were determined from Affymetrix Human Exon 1.0 ST microarray data using published methods. Results: 14% of the biopsy cores were predicted by the PORTOS signature to be more responsive to radiation therapy. Compared to the cores with average PORTOS scores, the “high PORTOS” biopsies showed a 2 fold or greater level of the tumor immunoactivation markers Act CD4, Act CD8, EC, HLA DPA1 and Tem CD8 and a 2 fold or lower level of the tumor immunosuppression markers MDSC, SC, TIM3 and T reg (Mann-Whitney P value of <0.0001 for all nine comparisons of medians). Discussion: Preliminary studies suggest that prostate cancers with PORTOS scores that predict greater sensitivity to radiation therapy also have immunophenotype profiles consistent with a higher level of overall immunogenicity. Citation Format: Sandra M. Gaston, Sanoj Punnen, Oleksandr Kryvenko, Alan Pollack, Elai Davicioni, Seagle Liu, Radka Stoyanova. Prostate cancer molecular immunophenotypes in biopsies with high vs average radiation sensitivity as predicted by post-operative radiation therapy outcomes (PORTOS) scores [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB065.