{"doi":"10.1093/jimmun/vkaf283.412","title":"Spatial proteomic analysis reveals vaccine and PD-1 blockade elicits changes to the prostate tumor immune microenvironment with infiltration of dendritic cells and activated CD8 T cells 2502","abstract":"Abstract Description We have previously shown in murine tumor models that PD-L1 blockade improves anti-tumor vaccine efficacy. In 66 patients with metastatic, castration-resistant prostate cancer, we reported that concurrent, but not sequential, treatment with DNA vaccine encoding prostatic acid phosphatase (pTVG-HP) and PD-1 blockade resulted in PSA declines in 35% (>50% declines in 10%) patients, reductions in tumor volumes, and 47.2% six-month progression free survival (PFS) rate [NCT02499835]. Immune-related adverse events (irAEs) correlated with prolonged stable disease or PSA declines. Tumor biopsies obtained pre- and post-treatment from the same metastatic sites of 12 patients were analyzed using Nanostring nCounter and GeoMx platforms. Responders (PSA ↓ >50% or PFS > 6 months) showed increased antigen presentation and T cell activation related marker expression, dendritic cell infiltration and reduced checkpoint marker expression. Non-responders exhibited immune-suppressive pathways, including higher expression of immune checkpoints and myeloid-derived suppressor cell (MDSC)-associated markers. Increased PARP expression in non-responders and in patients w/o irAEs suggested a potential resistance mechanism. These findings emphasize the role of tumor-infiltrating antigen presenting cells and T cell activation in therapeutic response to vaccine + PD-1 blockade and suggest that further combination with PARP inhibition or treatments targeting MDSC might increase treatment efficacy. Funding Sources Grant support was provided by NIH (P30 CA014520 and R01 CA129154), a 2014 Movember-PCF Challenge Award from the Prostate Cancer Foundation, and with funding support by Madison Vaccines, Inc. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)","journal":"The Journal of Immunology","year":2025,"id":582232,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":316490,"name":"Douglas G. McNeel","orcid":"0000-0003-1471-6723","position":1,"is_corresponding":false},{"id":492246,"name":"Ichwaku Rastogi","orcid":"0000-0003-1957-1164","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:55.657290Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}