Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non–small cell lung cancer

Eri Sugiyama, Yosuke Togashi, Yoshiko Takeuchi, Sayoko Shinya, Yasuko Tada, Keisuke Kataoka, Kenta Tane, Eiichi Sato, Genichiro Ishii, Koichi Goto, Yasushi Shintani, Meinoshin Okumura, Masahiro Tsuboi, Hiroyoshi Nishikawa

Research output: Contribution to journalArticlepeer-review

123 Citations (Scopus)


The clinical efficacy of anti–PD-1 (programmed cell death–1) monoclonal antibody (mAb) against cancers with oncogenic driver gene mutations, which often harbor a low tumor mutation burden, is variable, suggesting different contributions of each driver mutation to immune responses. Here, we investigated the immunological phenotypes in the tumor microenvironment (TME) of epidermal growth factor receptor (EGFR)–mutated lung adenocarcinomas, for which anti–PD-1 mAb is largely ineffective. Whereas EGFR-mutated lung adenocarcinomas had a noninflamed TME, CD4+ effector regulatory T cells, which are generally present in the inflamed TME, showed high infiltration. The EGFR signal activated cJun/cJun N-terminal kinase and reduced interferon regulatory factor–1; the former increased CCL22, which recruits CD4+ regulatory T cells, and the latter decreased CXCL10 and CCL5, which induce CD8+ T cell infiltration. The EGFR inhibitor erlotinib decreased CD4+ effector regulatory T cells infiltration in the TME and in combination with anti–PD-1 mAb showed better antitumor effects than either treatment alone. Our results suggest that EGFR inhibitors when used in conjunction with anti–PD-1 mAb could increase the efficacy of immunotherapy in lung adenocarcinomas.

Original languageEnglish
Article numbereaav3937
JournalScience Immunology
Issue number43
Publication statusPublished - 2020 Jan
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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