Journal article
IL-1α Expands SLC2A1highSPP1highIFNlow Myeloid Cells to Drive Immune Escape and Malignant Transformation of Pre-cancers
Cancer research (Chicago, Ill.)
07/14/2026
DOI: 10.1158/0008-5472.CAN-25-4416
PMID: 42446924
Abstract
Head and neck squamous cell carcinomas (HNSCC) are preceded by potentially malignant precursor lesions, highlighting the need for strategies to discern which precancerous lesions harbor a high risk for malignant transformation. Here, we developed a unique genetically engineered mouse model (GEMM) by inducing oral epithelial cell-specific amplification of Sox2, which recapitulates the malignant transformation of epithelial dysplasia to HNSCC with high histologic and phenotypic resemblance to human tumors. SOX2 promoted the release of IL-1α and CCL2, expanding inflammatory monocytes. The recruited myeloid cells exhibited a distinct, early, high-risk signature of high levels of IL-1α, SLC2A1, SPP1, and low levels of type-I interferon (IFN-I) targets, and intralesional SLC2A1high myeloid cells were more suppressive than their SLC2A1low counterparts. Brief priming of myeloid cells with IL-1α desensitized them to STING agonists and enhanced the suppressive effects of myeloid-derived suppressor cells on T-cell activation. Mechanistically, IL-1 activation repressed the expression of DHHC3/7 enzymes that palmitoylate STING. Early blockade of IL-1 signaling using pharmacologic and genetic approaches similarly reduced the most suppressive subsets of myeloid cells, promoted immune surveillance against the progression of epithelial dysplasia, and extended survival. This work establishes a central high-risk myeloid cell transcriptomic program, characterized by elevated levels of IL-1α, SLC2A1, and SPP1, that leads to irreversible immune escape upon transformation of precancerous epithelial lesions.
Details
- Title: Subtitle
- IL-1α Expands SLC2A1highSPP1highIFNlow Myeloid Cells to Drive Immune Escape and Malignant Transformation of Pre-cancers
- Creators
- Hülya Taner - University of MichiganWang Gong - The University of Texas MD Anderson Cancer CenterEmily A Lanzel - University of IowaKala Chand Debnath - The University of Texas MD Anderson Cancer CenterFelipe Nör - University of MichiganKohei Okuyama - The University of Texas MD Anderson Cancer CenterYuesong Wu - Michigan State UniversityCharisse A Ursin - The University of Texas MD Anderson Cancer CenterShajedul Islam - The University of Texas MD Anderson Cancer CenterXin Hu - The University of Texas MD Anderson Cancer CenterYumin He - The University of Texas MD Anderson Cancer CenterZackary R Fitzsimonds - The University of Texas MD Anderson Cancer CenterZaiye Li - The University of Texas MD Anderson Cancer CenterJung M Kuczura - University of MichiganSashider Rajesh - University of MichiganAndriana Manousidaki - Michigan State UniversityShuo Feng - University of MichiganMiki Lee - University of MichiganShadmehr Demehri - Massachusetts General HospitalHaitao Wen - The Ohio State UniversityAndrew G Sikora - The University of Texas MD Anderson Cancer CenterMark S Chambers - The University of Texas MD Anderson Cancer CenterJeffrey N Myers - The University of Texas MD Anderson Cancer CenterPeter J Polverini - University of MichiganJacques E Nör - University of MichiganSimon Young - The University of Texas Health Science Center at HoustonThomas D Wang - University of MichiganJianwen Que - Columbia University Irving Medical CenterJian Hu - The University of Texas MD Anderson Cancer CenterYuying Xie - Michigan State UniversityJames J Moon - University of MichiganYu Leo Lei - The University of Texas MD Anderson Cancer Center
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.)
- DOI
- 10.1158/0008-5472.CAN-25-4416
- PMID
- 42446924
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- American Association for Cancer Research
- Language
- English
- Electronic publication date
- 07/14/2026
- Academic Unit
- Oral Pathology, Radiology and Medicine
- Record Identifier
- 9985183395402771
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