Nature Communications (May 2021)

Th17 cells contribute to combination MEK inhibitor and anti-PD-L1 therapy resistance in KRAS/p53 mutant lung cancers

  • David H. Peng,
  • B. Leticia Rodriguez,
  • Lixia Diao,
  • Pierre-Olivier Gaudreau,
  • Aparna Padhye,
  • Jessica M. Konen,
  • Joshua K. Ochieng,
  • Caleb A. Class,
  • Jared J. Fradette,
  • Laura Gibson,
  • Limo Chen,
  • Jing Wang,
  • Lauren A. Byers,
  • Don. L. Gibbons

DOI
https://doi.org/10.1038/s41467-021-22875-w
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 15

Abstract

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Recent clinical trials combining MEK inhibitors with anti-PD-L1 in solid tumours show moderate responses. Here, the authors demonstrate that the combination of MEK inhibition and PD-L1 blockade in KRAS mutant lung cancer models leads to a transient tumour regressions and resistance due to increased infiltration of Th17 cells and that the triple therapy targeting MEK, PD-L1 and IL-17 produced better in vivo responses.