Journal Article

DKFZ-2026-01200

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Stimulator of interferon genes agonist augmented antitumor immunity of osimertinib in Egfr-mutated lung cancer.

Nishimura, J. ; Kuribayashi, T. ; Brägelmann, J. ; Okawa, S. ; Taoka, M. ; Mori, S. ; Nishimura, T. ; Tanaka, T. ; Makimoto, G. ; Ninomiya, K. ; Rai, K. ; Ichihara, E. ; Katayama, R. ; Hotta, K. ; Tabata, M. ; Togashi, Y. ; Maeda, Y. ; Sos, M. L.DKFZ* ; Kiura, K. ; Ohashi, K.

2026
John Wiley & Sons, Inc. Hoboken, NJ

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.

Keyword(s): CD8+ T cells ; EGFR mutation ; EGFR tyrosine kinase inhibitor ; NK cells ; abscopal effect ; stimulator of interferon genes

Note: epub

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Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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