当前位置: X-MOL 学术Sci. Immunol › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non-small cell lung cancer.
Science Immunology ( IF 17.6 ) Pub Date : 2020-01-31 , DOI: 10.1126/sciimmunol.aav3937
Eri Sugiyama 1, 2 , Yosuke Togashi 2 , Yoshiko Takeuchi 2 , Sayoko Shinya 2 , Yasuko Tada 2 , Keisuke Kataoka 3 , Kenta Tane 4 , Eiichi Sato 5 , Genichiro Ishii 6 , Koichi Goto 7 , Yasushi Shintani 8 , Meinoshin Okumura 8 , Masahiro Tsuboi 4 , Hiroyoshi Nishikawa 1, 2
Affiliation  

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.

中文翻译:

在EGFR突变的非小细胞肺癌中,EGFR的阻断改善了对PD-1阻断的反应性。

抗PD-1(程序性细胞死亡1)单克隆抗体(mAb)对具有致癌驱动基因突变的癌症(通常携带低的肿瘤突变负担)的临床疗效是可变的,表明每种驱动突变对免疫的贡献不同回应。在这里,我们调查了表皮生长因子受体(EGFR)突变的肺腺癌的肿瘤微环境(TME)中的免疫表型,其抗PD-1 mAb在很大程度上无效。EGFR突变的肺腺癌具有未发炎的TME,而通常存在于发炎的TME中的CD4 +效应子调节性T细胞表现出高度浸润。EGFR信号激活cJun / cJun N末端激酶并降低干扰素调节因子-1;前者增加CCL22,后者募集CD4 +调节性T细胞,后者降低CXCL10和CCL5,从而诱导CD8 + T细胞浸润。表皮生长因子受体抑制剂埃洛替尼可降低TME中CD4 +效应物调节性T细胞的浸润,与抗PD-1 mAb组合显示的抗肿瘤作用比任何一种单独治疗都更好。我们的结果表明,EGFR抑制剂与抗PD-1 mAb结合使用可提高免疫疗法在肺腺癌中的疗效。
更新日期:2020-02-03
down
wechat
bug