{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:47:19Z","timestamp":1792028839077,"version":"4.4.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pancreatic ductal adenocarcinoma (PDAC) remains largely resistant to immunotherapy, with response rates below 5%. Emerging evidence suggests that immune exclusion in PDAC is actively maintained by oncogenic KRAS signaling. Mechanistic studies implicate three coordinated processes: autophagy-mediated degradation of MHC-I and impaired antigen presentation, expansion of suppressive myeloid populations, and desmoplastic stromal remodeling that restricts cytotoxic T-cell access to malignant epithelium. These barriers are at least partially reversible. Inhibition of autophagy restores surface MHC-I expression and re-enables antigen-dependent CD8+ T-cell killing. Suppression of KRAS pathway signaling remodels the myeloid compartment, alters stromal architecture, and increases intratumoral CD8+ T-cell infiltration in experimental systems. Recent studies further demonstrate that combining allele-specific KRAS inhibition with multi-arm immunotherapy can produce durable responses in resistant PDAC models. Spatial profiling data also suggest that immune architecture differs by KRAS allele, with KRAS G12D tumors more frequently exhibiting stromal T-cell segregation and KRAS G12R tumors demonstrating altered immune proximity and metabolic dependence. Together, these findings support a model in which KRAS-targeted therapy functions not only as tumoricidal therapy but also as immune conditioning of the tumor microenvironment. Translating this biologic reversibility into durable clinical benefit will require rational, barrier-specific, and allele-informed combination strategies.<\/jats:p>","DOI":"10.1093\/oncolo\/oyag160","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:47:46Z","timestamp":1780055266000},"source":"Crossref","is-referenced-by-count":1,"title":["KRAS-driven immune exclusion in pancreatic ductal adenocarcinoma: mechanisms and therapeutic reversal"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8125-1727","authenticated-orcid":false,"given":"Kenneth A","family":"Kern","sequence":"first","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , San Diego, 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