Research ArticleCANCER IMMUNOLOGY

Hypofractionated EGFR tyrosine kinase inhibitor limits tumor relapse through triggering innate and adaptive immunity

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Science Immunology  09 Aug 2019:
Vol. 4, Issue 38, eaav6473
DOI: 10.1126/sciimmunol.aav6473

Enhanced inhibitor

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) block oncogenic receptor signaling and are used as a first-line treatment for EGFR-mutated non–small cell lung cancer. Resistance to EGFR TKIs, including the standard hyperfractionated EGFR TKI (HyperTKI) treatment, is a problem that has driven the development of next-generation inhibitors. Here, Liu et al. describe the improved efficacy of hypofractionated EGFR TKI (HypoTKI) relative to HyperTKI in triggering antitumor T cell responses and preventing relapse in a TKI-sensitive syngeneic murine tumor model through a mechanism involving the type I IFN and MyD88 signaling pathways. Coadministration of HypoTKI with an anti–PD-L1 antibody further improved antitumor responses and reduced tumor relapse, thus suggesting that this combined therapy may be a potential alternative to existing treatment regimens.

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