Limits tumor relapse through triggering innate and adaptive immunity

Zhida Liu, Chuanhui Han, Chunbo Dong, Aijun Shen, Eric Hsu, Zhenhua Ren, Changzheng Lu, Longchao Liu, Anli Zhang, Casey Timmerman, Yang Pu, Yang Wang, Mingyi Chen, Jian Qiao, Yang Xin Fu

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a first-line therapy for rapidly killing tumors such as those associated with non-small cell lung cancer by blocking oncogenic receptor signaling, but tumor relapse often occurs. Here, we have observed that hypofractionated EGFR TKI treatment (HypoTKI) is more potent than standard hyperfractionated EGFR TKI treatment (HyperTKI), and its antitumor effect associated with preventing tumor relapse depends on T cells. HypoTKI triggers greater innate sensing for type I IFN and CXCL10 production through the Myd88 signaling pathway to enhance tumor-specific T cell infiltration and reactivation. We also demonstrate that timely programmed cell death ligand-1 (PD-L1) blockade can synergize with HypoTKI to control advanced large tumors and effectively limit tumor relapse without severe side effects. Our study provides evidence for exploring the potential of a proper combination of EGFR TKIs and immunotherapy as a first-line treatment for treating EGFR-driven tumors.

Original languageEnglish (US)
Article numbereaav6473
JournalScience Immunology
Volume4
Issue number38
DOIs
StatePublished - Aug 9 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Limits tumor relapse through triggering innate and adaptive immunity'. Together they form a unique fingerprint.

  • Cite this

    Liu, Z., Han, C., Dong, C., Shen, A., Hsu, E., Ren, Z., Lu, C., Liu, L., Zhang, A., Timmerman, C., Pu, Y., Wang, Y., Chen, M., Qiao, J., & Fu, Y. X. (2019). Limits tumor relapse through triggering innate and adaptive immunity. Science Immunology, 4(38), [eaav6473]. https://doi.org/10.1126/sciimmunol.aav6473