Objective: To screen for possible therapeutic targets in prostate cancer immune microenvironment and to test if some of local ablative therapies can elicit abscopal effect in conjunction with immune check point blockade. Patients, Methods and Materials: 3 patients cohorts were used to identify potential therapeutic targets and to reconstruct their interactome. Association between candidate genes and oncological outcomes were established using the Kaplan Maier analysis and logistic regression. To test the abscopal effect FVB/NJ mice were injected subcutaneously into each flank with either 1∙106 or 0.2∙106 isogenic hormone sensitive Myc-Cap cells to establish synchronous grafts. Mice were treated with four intraperitoneal injections of anti-PD-1 (10mg/kg), anti-CTLA-4 (1mg/kg), or isotype control antibody with or without adjuvant ablation of the larger tumor graft and with or without neo-adjuvant androgen deprivation with degarelix (ADT). Mouse survival and growth rates of tumor grafts were measured. Results: B7-H3 expression was present in the majority of localized prostate cancer cases and was positively associated with Gleason score (p<0.001), tumor stage (p <0.02), and castrate resistant metastatic disease (p<0.0001). Within prostatectomy tissue, high B7-H3 expression correlated with the development of metastasis and prostate cancer specific mortality, but this was not significant on multi-variable analysis. B7-H3 expression correlated with ERG+ disease (r = 0.99) and AR expression (r=0.36). ChIP analysis revealed AR binding upstream of B7-H3, suggesting potential androgen dependent regulation. Gene set enrichment analysis also demonstrated an association of B7-H3 with androgen signaling as well as immune regulatory pathways. Treatment with anti-CTLA-4 antibody and cryoablation delayed the growth of the distant tumor by 14.8 days (p=0.0006) and decreased the mortality rate by factor of 4 (p=0.0003) when compared to cryoablation alone. Combining PD-1 blockade with cryoablation did not show a benefit over use of either treatment alone. Addition of ADT to anti-PD1 therapy and cryoablation doubled the time to accelerated growth in the untreated tumors (p=0.0021) and extended survival when compared to cryoablation combined with ADT in 25% of the mice. Effects of combining anti-PD1 with ADT and cryoablation on mouse survival were obviated by T cell depletion. Conclusion: B7-H3 expression correlates with high Gleason grade and advanced prostate cancer stage with higher expression portending poor oncologic outcomes in prostatectomy cohorts. B7-H3 expression appears to related to androgen signaling as well as the immune reactome. Trimodal therapy consisting of androgen deprivation, cryoablation and PD-1 blockade as well as the combination of cryoablation and low dose anti-CTLA-4 blockade showed that local therapies with cryoablation could be considered to augment the effects of checkpoint blockade in prostate cancer.