{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T02:42:29Z","timestamp":1770432149506,"version":"3.49.0"},"reference-count":91,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004881","name":"Instituto Mexicano del Seguro Social","doi-asserted-by":"publisher","award":["R-2023-785-025"],"award-info":[{"award-number":["R-2023-785-025"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prostate cancer remains largely refractory to immunotherapy, implying the existence of context-specific immune landscape programs that diverge between circulation and tumor. Here, we integrate bulk RNA sequencing from three cohorts (patient peripheral mononuclear cells, primary prostate tissue, and biochemical-recurrence tumors) with multiparameter flow cytometry, unsupervised UMAP\/T-REX (Tracking Responders Expanding) mapping, and de novo discovery of long non-coding RNAs (lncRNAs) to characterize context-specific immunoregulation. Patient PBMCs revealed a coherent IL-1\/TNF\/IL-17 inflammatory architecture with strong chemotactic programs and an unexpected neutrophil-like signal despite density-gradient isolation, consistent with low-density PMN-MDSCs. In contrast, tumors broadly repressed chemokines and innate immune mediators, yet upregulated prostate cancer-associated lncRNAs, indicating local immune quiescence coupled with non-coding regulatory programs. Recurrent tumors acquired epithelial\u2013mesenchymal transition and metabolic remodeling, accompanied by relapse-associated lncRNA signatures, whereas long-term nonrecurrent tumors preserved epithelial and stress-response networks. High-dimensional cytometry confirmed discrete, cancer-enriched myeloid clusters expressing CD47, SIRP\u03b1, PD-L1, CD73, and Galectin-9. Network analysis highlighted inflammatory hubs (CXCL2, PTGS2) in PBMCs and loss of mechanotransduction modules in tumors. Structural modeling uncovered a three-way junction and 3\u2032 triple helix in lncRNA. Collectively, these data suggest that circulating inflammatory rewiring is associated with checkpoint-rich suppressor expansion and tumor immune quiescence, outlining integrated myeloid- and RNA-directed strategies for cancer research.<\/jats:p>","DOI":"10.3390\/ijms27031511","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T16:46:28Z","timestamp":1770137188000},"page":"1511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prostate Cancer: Dissecting Novel Immunosuppressive Mechanisms Through Context-Specific Transcriptomic Programs and MDSC Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2755-3302","authenticated-orcid":false,"given":"Pedro","family":"Reyes Martinez","sequence":"first","affiliation":[{"name":"Doctorado en Ciencias Biom\u00e9dicas, Departamento de Fisiolog\u00eda, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44350, Mexico"},{"name":"Divisi\u00f3n de Epidemiolog\u00eda, Unidad M\u00e9dica de Alta Especialidad (UMAE), Hospital de Especialidades (HE), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44329, Mexico"},{"name":"Divisi\u00f3n de Inmunolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erick","family":"Sierra Diaz","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Epidemiolog\u00eda, Unidad M\u00e9dica de Alta Especialidad (UMAE), Hospital de Especialidades (HE), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44329, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4675-2203","authenticated-orcid":false,"given":"Fabiola","family":"Solorzano Ibarra","sequence":"additional","affiliation":[{"name":"Estancias Posdoctorales Secihti, Guadalajara 44340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9211-8572","authenticated-orcid":false,"given":"Jorge Raul","family":"Vazquez Urrutia","sequence":"additional","affiliation":[{"name":"Department of Medicine, The Pennsylvania State University College of Medicine, The Pennsylvania State University, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 de Jes\u00fas","family":"Guerrero Garc\u00eda","sequence":"additional","affiliation":[{"name":"Banco de Sangre Central, Unidad M\u00e9dica de Alta Especialidad (UMAE), Hospital de Especialidades (HE), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44329, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-1397","authenticated-orcid":false,"given":"Martha Cecilia","family":"T\u00e9llez Ba\u00f1uelos","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Traslacional, Departamento de Biolog\u00eda Celular y Molecular, Centro Universitario de Ciencias Biol\u00f3gicas y Agropecuarias, Universidad de Guadalajara, Zapopan 45200, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2124-2036","authenticated-orcid":false,"given":"Julio Enrique","family":"Casta\u00f1eda Delgado","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social (IMSS), Zacatecas 98000, Mexico"},{"name":"Investigadores por M\u00e9xico, C\u00e1tedras Secihti, Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social (IMSS), Zacatecas 98000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-0293","authenticated-orcid":false,"given":"Karina","family":"Sanchez Reyes","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednicas M\u00e9dicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44350, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9045-7052","authenticated-orcid":false,"given":"Pablo Cesar","family":"Ortiz Lazareno","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Inmunolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO), Centro M\u00e9dico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.eururo.2023.04.021","article-title":"2022 Update on Prostate Cancer Epidemiology and Risk Factors\u2014A Systematic Review","volume":"84","author":"Bergengren","year":"2023","journal-title":"Eur. 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