2. Academic Validation
  3. Stimulator of interferon genes agonist augmented antitumor immunity of osimertinib in Egfr-mutated lung cancer

Stimulator of interferon genes agonist augmented antitumor immunity of osimertinib in Egfr-mutated lung cancer

  • Mol Oncol. 2026 May 21. doi: 10.1002/1878-0261.70264.
Jun Nishimura 1,  Tadahiro Kuribayashi 1,  Johannes Brägelmann 2 3 4,  Sachi Okawa 1,  Masataka Taoka 1,  Shunta Mori 1,  Tomoka Nishimura 1,  Takaaki Tanaka 1,  Go Makimoto 5,  Kiichiro Ninomiya 6,  Kammei Rai 7,  Eiki Ichihara 8,  Ryohei Katayama 9 10,  Katsuyuki Hotta 7,  Masahiro Tabata 8,  Yosuke Togashi 5,  Yoshinobu Maeda 1,  Martin L Sos 2 11 12 13,  Katsuyuki Kiura 5,  Kadoaki Ohashi 5
Affiliations

Affiliations

  • 1 Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
  • 2 Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Germany.
  • 3 Faculty of Medicine and University Hospital Cologne, Mildred Scheel School of Oncology, University of Cologne, Germany.
  • 4 Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, Germany.
  • 5 Department of Respiratory Medicine, Okayama University Hospital, Japan.
  • 6 Center for Comprehensive Genomic Medicine, Okayama University Hospital, Japan.
  • 7 Center for Innovative Clinical Medicine, Okayama University Hospital, Japan.
  • 8 Center for Clinical Oncology, Okayama University Hospital, Japan.
  • 9 Division of Experimental Chemotherapy, Cancer Chemotherapy Centre, Japanese Foundation for Cancer Research, Tokyo, Japan.
  • 10 Department of Computational Biology and Medical Science, Graduate School of Frontier Science, Tokyo, The University of Tokyo, Japan.
  • 11 Department of Translational Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 12 German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between DKFZ and Ludwig-Maximilians-Universität Munich, Germany.
  • 13 Department of Medicine III, LMU University Hospital Munich, Germany.
PMID: 42169500 DOI: 10.1002/1878-0261.70264
Abstract

Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers (NSCLCs) lack effective immunotherapy due to a noninflamed tumor microenvironment (TME). We previously reported that EGFR tyrosine-kinase-inhibitor (TKI) induced CD8+ T-cell immunity, which was insufficient for tumor eradication. We evaluated the potential of combining EGFR-TKI with stimulator of interferon genes (STING) agonists in activating a systemic antitumor response. Using a syngeneic mouse model of genetically engineered Egfr-mutant NSCLC, we evaluated the antitumor effects of STING agonist ADU-S100, alone and combined with osimertinib. Immunohistochemistry and flow cytometry were used to assess the TME. Osimertinib alone enhanced CD8+ T-cell infiltration but not Natural Killer (NK) cell infiltration. ADU-S100 injection alone modestly suppressed tumor growth with increasing CD8+/NK cell infiltration in the TME, but lacked an abscopal effect. Combining ADU-S100 with osimertinib significantly enhanced the antitumor effects and CD8+/NK cell infiltration. Depletion of either CD8+ or NK cells reduced the combination effect. Crucially, the combination induced an abscopal effect accompanied by PD-1+/CD8+ cell infiltration. Combining osimertinib with a STING agonist augmented innate and adaptive immunity, inducing systemic antitumor responses in EGFR-mutant NSCLC.

Keywords

CD8+ T cells; EGFR mutation; EGFR tyrosine kinase inhibitor; NK cells; abscopal effect; stimulator of interferon genes.

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