| Literature DB >> 35121903 |
Víctor A Arrieta1,2, Andrew X Chen3, J Robert Kane1, Seong Jae Kang1, Cynthia Kassab4, Crismita Dmello1, Junfei Zhao3,5, Kirsten B Burdett6, Pavan S Upadhyayula7, Catalina Lee-Chang1, Joseph Shilati1, Dinesh Jaishankar8, Li Chen1, Andrew Gould1, Daniel Zhang1, Jinzhou Yuan5, Wenting Zhao5, Xiaoyang Ling4, Jared K Burks9, Brice Laffleur10, Christina Amidei1, Jeffrey N Bruce7, Rimas V Lukas11, Jonathan T Yamaguchi1, David Cieremans12, Gerson Rothschild13, Uttiya Basu13, Matthew McCord14, Daniel J Brat14, Hui Zhang6, Lee A D Cooper14, Bin Zhang15, Peter Sims5, Tim F Cloughesy16, Robert Prins16, Peter Canoll17, Roger Stupp1,11,18, Amy B Heimberger1, Craig Horbinski1,14, Fabio M Iwamoto19, Raul Rabadan20,21, Adam M Sonabend22.
Abstract
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.Entities:
Mesh：
Year: 2021 PMID： 35121903 PMCID： PMC8818262 DOI： 10.1038/s43018-021-00260-2
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347