{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:25:32Z","timestamp":1787585132223,"version":"build-2736575974"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Oncogenic\n                    <jats:italic>KRAS<\/jats:italic>\n                    mutations rank among the most prevalent driver alterations in human malignancies, reaching near-universal frequency (~98%) in pancreatic ductal adenocarcinoma (PDAC) and high prevalence in colorectal cancer (CRC, ~52%) and lung adenocarcinoma (LAC, ~32%). Beyond their canonical roles in promoting cell-intrinsic proliferation and survival through the MAPK\/ERK and PI3K\/AKT cascades, KRAS mutations actively sculpt a profoundly immunosuppressive tumor microenvironment (TME), which constitutes a major barrier to both targeted therapy and immunotherapy. Through coordinated programs encompassing inflammatory cytokine secretion, downregulation of antigen presentation machinery, tumor-associated macrophage (TAM) reprogramming, myeloid-derived suppressor cell (MDSC) expansion, and PD-L1 upregulation, KRAS-mutant tumors establish robust immune exclusion. These programs are further stratified by co-mutations in\n                    <jats:italic>STK11<\/jats:italic>\n                    ,\n                    <jats:italic>KEAP1<\/jats:italic>\n                    , and\n                    <jats:italic>TP53<\/jats:italic>\n                    , which define distinct immune phenotypes ranging from inflamed to profoundly immune-excluded \u201ccold\u201d tumors. The recent approval of covalent KRAS G12C inhibitors, sotorasib and adagrasib, has revealed that targeted KRAS blockade can remodel the TME toward an immunostimulatory state, providing a mechanistic rationale for combining KRAS-directed agents with immune checkpoint blockade, STING agonists, and neoantigen vaccines. This mini-review synthesizes the current knowledge of KRAS-immune crosstalk, highlights existing controversies and research gaps, and evaluates emerging combination strategies designed to convert immune exclusion into durable anti-tumor immunity.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1933939","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:41:11Z","timestamp":1787582471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["KRAS mutations as architects of the tumor immune microenvironment: implications for combination therapies"],"prefix":"10.3389","volume":"16","author":[{"given":"Vasudevan","family":"Ramachandran","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Faculty of Health Sciences, MAIWP International University, Taman Batu Muda, Batu Caves","place":["Kuala Lumpur, Malaysia"]},{"name":"Department of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University","place":["Chennai, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haily Liduin","family":"Koyou","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Faculty of Health Sciences, MAIWP International University, Taman Batu Muda, Batu Caves","place":["Kuala Lumpur, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddarth","family":"Raajasekar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, KIT-Kalaignar Karunanidhi Institute of Technology, Coimbatore","place":["Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Hazmi Bin","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang","place":["Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyana Najwa Binti","family":"Inche Mat","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang","place":["Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkataramanan","family":"Swaminathan","sequence":"additional","affiliation":[{"name":"Department of Diagnostic & Allied Health Sciences, Management & Science University, University Drive, Off Persiaran Olahraga, Shah Alam","place":["Selangor, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Nazil","family":"Salleh","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Faculty of Health Sciences, MAIWP International University, Taman Batu Muda, Batu Caves","place":["Kuala Lumpur, Malaysia"]},{"name":"Chancellery Office, Saito University College, 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