ERK1/2 phosphorylation predicts survival following anti-PD-1 immunotherapy in recurrent glioblastoma - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Nature Cancer Année : 2021

ERK1/2 phosphorylation predicts survival following anti-PD-1 immunotherapy in recurrent glioblastoma

Fabio M. Iwamoto
  • Fonction : Auteur correspondant
Raul Rabadan
  • Fonction : Auteur correspondant

Résumé

Only a subset of recurrent glioblastoma (rGBM) responds to anti-PD-1 immunotherapy. Previously, we reported enrichment of BRAF/PTPN11 mutations in 30% of rGBM that responded to PD-1 blockade. Given that BRAF and PTPN11 promote MAPK/ERK signaling, we investigated whether activation of this pathway is associated with response to PD-1 inhibitors in rGBM, including patients that do not harbor BRAF/PTPN11 mutations. Here we show that immunohistochemistry for ERK1/2 phosphorylation (p-ERK), a marker of MAPK/ERK pathway activation, is predictive of overall survival following adjuvant PD-1 blockade in two independent rGBM patient cohorts. Single-cell RNA-sequencing and multiplex immunofluorescence analyses revealed that p-ERK was mainly localized in tumor cells and that high-p-ERK GBMs contained tumor-infiltrating myeloid cells and microglia with elevated expression of MHC class II and associated genes. These findings indicate that ERK1/2 activation in rGBM is predictive of response to PD-1 blockade and is associated with a distinct myeloid cell phenotype.

Dates et versions

hal-03512180 , version 1 (05-01-2022)

Identifiants

Citer

Victor A. Arrieta, Andrew X. Chen, J. Robert Kane, Seong Jae Kang, Cynthia Kassab, et al.. ERK1/2 phosphorylation predicts survival following anti-PD-1 immunotherapy in recurrent glioblastoma. Nature Cancer, 2021, 2 (12), pp.1372-+. ⟨10.1038/s43018-021-00260-2⟩. ⟨hal-03512180⟩
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