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

Autor: Arrieta VA; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; PECEM, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico., Chen AX; Program for Mathematical Genomics, Department of Systems Biology, Columbia University, New York, NY, USA., Kane JR; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Kang SJ; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Kassab C; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Dmello C; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Zhao J; Program for Mathematical Genomics, Department of Systems Biology, Columbia University, New York, NY, USA.; Department of Biomedical Informatics, Columbia University, New York, NY, USA., Burdett KB; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Upadhyayula PS; Department of Neurosurgery, Columbia University, New York, NY, USA., Lee-Chang C; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Shilati J; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Jaishankar D; Robert Lurie Comprehensive Cancer Center and Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Chen L; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Gould A; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Zhang D; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Yuan J; Department of Biomedical Informatics, Columbia University, New York, NY, USA., Zhao W; Department of Biomedical Informatics, Columbia University, New York, NY, USA., Ling X; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Burks JK; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Laffleur B; INSERM U1236, University of Rennes 1, Etablissement Français du Sang, Rennes, France., Amidei C; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Bruce JN; Department of Neurosurgery, Columbia University, New York, NY, USA., Lukas RV; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Yamaguchi JT; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Cieremans D; Department of Neurology, Columbia University, Vagelos College of Physicians and Surgeons Columbia University Irving Medical Center, New York, NY, USA., Rothschild G; Department of Microbiology and Immunology, Columbia University, New York, NY, USA., Basu U; Department of Microbiology and Immunology, Columbia University, New York, NY, USA., McCord M; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Brat DJ; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Zhang H; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Cooper LAD; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Zhang B; Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Sims P; Department of Biomedical Informatics, Columbia University, New York, NY, USA., Cloughesy TF; Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA., Prins R; Department of Medical and Molecular Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA., Canoll P; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA., Stupp R; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Heimberger AB; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Horbinski C; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Iwamoto FM; Department of Neurology, Columbia University, Vagelos College of Physicians and Surgeons Columbia University Irving Medical Center, New York, NY, USA. fi2146@cumc.columbia.edu., Rabadan R; Program for Mathematical Genomics, Department of Systems Biology, Columbia University, New York, NY, USA. rr2579@cumc.columbia.edu.; Department of Biomedical Informatics, Columbia University, New York, NY, USA. rr2579@cumc.columbia.edu., Sonabend AM; Department of Neurosurgery, Lou and Jean Malnati Brain Tumor Institute, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. adam.sonabend@northwestern.edu.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2021 Dec; Vol. 2 (12), pp. 1372-1386. Date of Electronic Publication: 2021 Nov 29.
DOI: 10.1038/s43018-021-00260-2
Abstrakt: 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.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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