{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T07:32:44Z","timestamp":1789889564125,"version":"4.0.1"},"reference-count":59,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023735","name":"Necsa","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100023735","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04a711r87","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Prostate cancer (PCa) is immunologically \u201ccold\u201d and resistant to immune checkpoint blockade (ICB), yet bulk analyses show low, non-prognostic PD-L1 expression. We hypothesised that this paradox reflects two overlooked dimensions: basal heterogeneity (static engine) and IFN-\u03b3-driven adaptive resistance (adaptive engine). Using TCGA-PRAD data (n=554) to parameterise an agent-based model, we simulated clonal selection and extended it to a hybrid discrete-continuum framework with reaction-diffusion IFN-\u03b3. Bulk PD-L1 was low (median 1.48 TPM) and non-prognostic (HR =1.15, p=0.621). The static engine alone produced weak immunoediting (1.10-fold enrichment), whereas the adaptive engine drove a 2.95-fold enrichment of PD-L1-high clones via protective sanctuary formation, without increasing final tumour burden. Induction knockout (Pmax=0) abrogated this advantage, while diffusion knockout (D=0) had no effect. The cold tumour paradox is resolved by a hierarchical twin engine: rare genomic outliers permit initial persistence, but local IFN-\u03b3\/PD-L1 feedback dominates resistance, identifying induction capacity as the primary therapeutic target for JAK\/STAT inhibition combined with ICB.<\/jats:p>","DOI":"10.3390\/biology15100806","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune Evasion in Prostate Cancer: Resolving the Cold Tumour Paradox via a Hybrid Discrete\u2013Continuum Computational Framework"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2742-3233","authenticated-orcid":false,"given":"Andile Kenneth","family":"Ntlokwana","sequence":"first","affiliation":[{"name":"Research and Innovation Division, South African Nuclear Energy Corporation, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5479-9255","authenticated-orcid":false,"given":"Edinah","family":"Mudimu","sequence":"additional","affiliation":[{"name":"Department of Decision Sciences, University of South Africa, Pretoria 0002, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6400-8867","authenticated-orcid":false,"given":"Monde McMillan","family":"Ntwasa","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, University of South Africa, Pretoria 0002, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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