SlideShare a Scribd company logo
1 of 18
Download to read offline
Víctor Andrés Arrieta González
MD,PhD
Exploring Predictive
Biomarkers and ERK1/2
Phosphorylation: A New
Horizon in Forecasting Survival
and Response to Immune
Checkpoint Blockade in
Glioblastoma Treatment
Clinical GBM responder and non-responder to PD-1 blockade
49.4 0.11
16.7
33.8
0 10
3
10
4
CD4 APC-Cy7
0
10
3
10
4
CD8
PE-Cy7-A
74.2 0.54
18.4
6.91
0 10
3
10
4
Comp-APC-Cy7-A
0
10
3
10
4
Comp-PE-Cy7-A
38.4 0.12
56.8
4.72
0 10
3
10
4
CD4 APC-Cy7
0
10
3
10
4
CD8
PE-Cy7
Start of
anti-PD-1
therapy
Start of
anti-PD-1
therapy
Last seen
alive 21
months after
PD-1 blockade
2 weeks 10 months 11 months 13 months 15 months
Resection
Resection
Resection
2 months Death 6
months
after PD-1
blockade
Recurrence
Recurrence
Responder
Non-responder
CD3 Blood Resected tissue
CSF
200 µm
Arrieta VA, Chen AX, et al, Nat Cancer 2021
Enrichment of BRAF/PTPN11 mutations in responder patients
Zhao J et al, Nat Med 2019
MAPK pathway
Pratilas CA et al, Clin Cancer Res 2010
PTPN11
p-ERK is associated with longer survival in recurrent GBM patients treated with
anti-PD-1 therapy
250 µm 250 µm
High p-ERK Low p-ERK
Arrieta VA, Chen AX, et al, Nat Cancer 2021
Patients with longer overall survival exhibited high levels of p-ERK regardless
of the genetic status of the BRAF/PTPN11
Arrieta VA, Chen AX, et al, Nat Cancer 2021
Cloughesy TF et al, Nat Med 2019
p-ERK is associated with overall survival in an independent cohort of
recurrent GBM patients treated with adjuvant PD-1 blockade
Arrieta VA, Chen AX, et al, Nat Cancer 2021
p-ERK is predominantly expressed by GBM cells
p-ERK
IHC
H&E
p-ERK
IHC
H&E
p-ERK
IHC
H&E
BRAFV600E
mutant GBM
High p-ERK
Wild-type BRAF
GBM
High p-ERK
Wild-type
BRAF GBM
Low p-ERK
200 µm 200 µm
200 µm 200 µm
200 µm 200 µm
p-ERK
SOX2 DAPI CD163 DAPI
SOX2 TMEM119
p-ERK
SOX2 DAPI CD163 DAPI
SOX2 TMEM119
p-ERK
SOX2 DAPI CD163 DAPI
SOX2 TMEM119
Arrieta VA, Chen AX, et al, Nat Cancer 2021
High-p-ERK GBMs contain abundant TMEM119+ microglia
p-ERK Iba1
250 µm 250 µm
Arrieta VA, Chen AX, et al, Nat Cancer 2021
TMEM119+ microglia are closer to SOX2+ p-ERK+ cells
TMEM119+ cells
CD163+ cells
SOX2+ p-ERK+
cells
Mean distance to the
nearest neighbor
From
To
SOX2+ p-ERK-
cells
TMEM119+ SOX2+ p-ERK+ TMEM119+ SOX2+ p-ERK+
High p-ERK Low p-ERK
200 µm 200 µm
Arrieta VA, Chen AX, et al, Nat Cancer 2021
CD163+ cells
GFAP+ p-ERK-
cells
Mean distance to the
nearest neighbor
From
To
GFAP+ p-ERK+
cells
Arrieta VA, Chen AX, et al, Nat Cancer 2021
CD163+ GFAP+ pERK+
CD163+ GFAP+ pERK+
High p-ERK Low p-ERK
200 µm 200 µm
CD163+ myeloid cells are closer to GFAP+ p-ERK+ cells
Analysis of GBM-infiltrating microglia and macrophages by single-cell RNA-seq
Arrieta VA, Chen AX, et al, Nat Cancer 2021
Myeloid cells from high p-ERK GBMs
have increased MHC II expression
Arrieta VA, Chen AX, et al, Nat Cancer 2021
GO
MHC
Class
II
protein
Complex
Binding
1.75
1.50
1.25
1.00
0.00
0.75
0.50
0.25
GO MHC Class II protein Complex Binding
0.8
0.6
0.4
0.2
0.0
1.0
0.5
0.0
-0.5
0 5000 10000 15000 20000 25000
High p-ERK
Low p-ERK
Myeloid cells from high p-ERK GBMs
have increased MHC II expression
Arrieta VA, Chen AX, et al, Nat Cancer 2021
• ERK1/2 phosphorylation shows that is a predictive biomarker of immune checkpoint
blockade including anti-PD-1 therapy in three independent cohorts of recurrent GBM
patients.
• GBMs that exhibit high numbers of p-ERK+ cells contain abundant TMEM119+ microglia.
• Myeloid cells derived from high p-ERK GBMs exhibit increased MHC class II expression
compared to myeloid cells derived from low p-ERK GBMs.
Conclusions
• There are several aspects to consider before implementing p-ERK as a biomarker for
response to anti-PD-1 therapy:
• Further validation in additional clinical cohorts
• Cut point value optimization
• Alternative techniques for MAPK pathway activation
• Standardized protocols for p-ERK assessment
Considerations
Acknowledgments
Columbia University
• Junfei Zhao
• David Cieremans
• Pavan
Upadhyayula
• Jinzhou Yuan
• Wenting Zhao
• Brice Laffleur
• Uttiya Basu
• Gerson Rothschild
• Peter Sims
• Peter Canoll
• Jeffrey N. Bruce
Northwestern University
• Seong Jae Kang
• Kirsten B. Burdett
• Crismita Dmello
• Andrew Gould
• Matthew McCord
• Li Chen
• Daniel Zhang
• Dinesh Jaishankar
• Joseph Shilati
• Christina Amidei
• Lee D Cooper
• Rimas V. Lukas
• Hui Zhang
• Jonathan T.
Yamaguchi
• Daniel J. Brat
• Bin Zhang
• Roger Stupp
MD Anderson Cancer Center
• Cynthia Kassab
• Xiaoyang Ling
• Jared K. Burks
UCLA
• Robert Prins
• Tim F.
Cloughesy
Andrew X. Chen J. Robert Kane
Adam Sonabend Fabio M. Iwamoto
Raul Rabadan
Amy Heimberger Craig Horbinski Catalina Lee Chang

More Related Content

Similar to Exploring Predictive Biomarkers and ERK1/2 Phosphorylation: A New Horizon in Forecasting Survival and Response to Immune Checkpoint Blockade in Glioblastoma Treatment

Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2
Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2
Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2QIAGEN
 
Target Validation / Biochemical and Cellular Assay Development
Target Validation / Biochemical and Cellular Assay Development Target Validation / Biochemical and Cellular Assay Development
Target Validation / Biochemical and Cellular Assay Development OSUCCC - James
 
In Vitro Characterization of a Novel Cis-acting Element (NCE) in the Cd4 Locus
In Vitro Characterization of a Novel Cis-acting Element (NCE) in the Cd4 Locus In Vitro Characterization of a Novel Cis-acting Element (NCE) in the Cd4 Locus
In Vitro Characterization of a Novel Cis-acting Element (NCE) in the Cd4 Locus Yordan Penev
 
Cupid Peptides presentation wjr
Cupid Peptides presentation wjrCupid Peptides presentation wjr
Cupid Peptides presentation wjrCupid Peptides
 
Recurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive Care
Recurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive CareRecurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive Care
Recurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive Carei3 Health
 
Sigma xi presentation
Sigma xi presentationSigma xi presentation
Sigma xi presentationedonoway
 
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...Dexter Hadley
 
Gold Nanoparticle/Interferon Conjugates as Directed Drug Delivery Mechanisms
Gold Nanoparticle/Interferon Conjugates as Directed Drug Delivery MechanismsGold Nanoparticle/Interferon Conjugates as Directed Drug Delivery Mechanisms
Gold Nanoparticle/Interferon Conjugates as Directed Drug Delivery Mechanismsedonoway
 
Sigma xi presentation
Sigma xi presentationSigma xi presentation
Sigma xi presentationedonoway
 
Circ ldlrad3 regulates cell proliferation, migration and invasion of pancreat...
Circ ldlrad3 regulates cell proliferation, migration and invasion of pancreat...Circ ldlrad3 regulates cell proliferation, migration and invasion of pancreat...
Circ ldlrad3 regulates cell proliferation, migration and invasion of pancreat...Clinical Surgery Research Communications
 
Choueiri nivo inrcc-009_presentation@asco2015
Choueiri nivo inrcc-009_presentation@asco2015Choueiri nivo inrcc-009_presentation@asco2015
Choueiri nivo inrcc-009_presentation@asco2015Danilo Baltazar Chacon
 
First-in-Human Chimeric antigen receptor (CAR) T cell Therapies: Promises and...
First-in-Human Chimeric antigen receptor (CAR) T cell Therapies: Promises and...First-in-Human Chimeric antigen receptor (CAR) T cell Therapies: Promises and...
First-in-Human Chimeric antigen receptor (CAR) T cell Therapies: Promises and...Prof. Eric Raymond Oncologie Medicale
 
Cellular therapies in Acute Lymphocytic Leukemia
Cellular therapies in Acute Lymphocytic LeukemiaCellular therapies in Acute Lymphocytic Leukemia
Cellular therapies in Acute Lymphocytic Leukemiaspa718
 

Similar to Exploring Predictive Biomarkers and ERK1/2 Phosphorylation: A New Horizon in Forecasting Survival and Response to Immune Checkpoint Blockade in Glioblastoma Treatment (20)

Plos
PlosPlos
Plos
 
Osp2 brennan SGC
Osp2 brennan SGCOsp2 brennan SGC
Osp2 brennan SGC
 
Nous reptes de la Medicina de Precisió
Nous reptes de la Medicina de PrecisióNous reptes de la Medicina de Precisió
Nous reptes de la Medicina de Precisió
 
Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2
Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2
Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2
 
Target Validation / Biochemical and Cellular Assay Development
Target Validation / Biochemical and Cellular Assay Development Target Validation / Biochemical and Cellular Assay Development
Target Validation / Biochemical and Cellular Assay Development
 
In Vitro Characterization of a Novel Cis-acting Element (NCE) in the Cd4 Locus
In Vitro Characterization of a Novel Cis-acting Element (NCE) in the Cd4 Locus In Vitro Characterization of a Novel Cis-acting Element (NCE) in the Cd4 Locus
In Vitro Characterization of a Novel Cis-acting Element (NCE) in the Cd4 Locus
 
Cupid Peptides presentation wjr
Cupid Peptides presentation wjrCupid Peptides presentation wjr
Cupid Peptides presentation wjr
 
Recurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive Care
Recurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive CareRecurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive Care
Recurrent/Metastatic HNSCC: Harnessing Immunotherapy in Comprehensive Care
 
2013 10 23_dna_for_dummies_v_presented
2013 10 23_dna_for_dummies_v_presented2013 10 23_dna_for_dummies_v_presented
2013 10 23_dna_for_dummies_v_presented
 
Sigma xi presentation
Sigma xi presentationSigma xi presentation
Sigma xi presentation
 
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...
 
Gold Nanoparticle/Interferon Conjugates as Directed Drug Delivery Mechanisms
Gold Nanoparticle/Interferon Conjugates as Directed Drug Delivery MechanismsGold Nanoparticle/Interferon Conjugates as Directed Drug Delivery Mechanisms
Gold Nanoparticle/Interferon Conjugates as Directed Drug Delivery Mechanisms
 
Sigma xi presentation
Sigma xi presentationSigma xi presentation
Sigma xi presentation
 
Brian_Strahl 2013_class_on_genomics_and_proteomics
Brian_Strahl 2013_class_on_genomics_and_proteomicsBrian_Strahl 2013_class_on_genomics_and_proteomics
Brian_Strahl 2013_class_on_genomics_and_proteomics
 
Circ ldlrad3 regulates cell proliferation, migration and invasion of pancreat...
Circ ldlrad3 regulates cell proliferation, migration and invasion of pancreat...Circ ldlrad3 regulates cell proliferation, migration and invasion of pancreat...
Circ ldlrad3 regulates cell proliferation, migration and invasion of pancreat...
 
Clinical Trials for Brain Tumor Patients
Clinical Trials for Brain Tumor PatientsClinical Trials for Brain Tumor Patients
Clinical Trials for Brain Tumor Patients
 
Choueiri nivo inrcc-009_presentation@asco2015
Choueiri nivo inrcc-009_presentation@asco2015Choueiri nivo inrcc-009_presentation@asco2015
Choueiri nivo inrcc-009_presentation@asco2015
 
First-in-Human Chimeric antigen receptor (CAR) T cell Therapies: Promises and...
First-in-Human Chimeric antigen receptor (CAR) T cell Therapies: Promises and...First-in-Human Chimeric antigen receptor (CAR) T cell Therapies: Promises and...
First-in-Human Chimeric antigen receptor (CAR) T cell Therapies: Promises and...
 
Cellular therapies in Acute Lymphocytic Leukemia
Cellular therapies in Acute Lymphocytic LeukemiaCellular therapies in Acute Lymphocytic Leukemia
Cellular therapies in Acute Lymphocytic Leukemia
 
CDAC 2018 Boeva discovery
CDAC 2018 Boeva discoveryCDAC 2018 Boeva discovery
CDAC 2018 Boeva discovery
 

More from InsideScientific

Next-Generation Safety Assessment Tools for Advancing In Vivo to In Vitro Tra...
Next-Generation Safety Assessment Tools for Advancing In Vivo to In Vitro Tra...Next-Generation Safety Assessment Tools for Advancing In Vivo to In Vitro Tra...
Next-Generation Safety Assessment Tools for Advancing In Vivo to In Vitro Tra...InsideScientific
 
A Ready-to-Analyze High-Plex Spatial Signature Development Workflow for Cance...
A Ready-to-Analyze High-Plex Spatial Signature Development Workflow for Cance...A Ready-to-Analyze High-Plex Spatial Signature Development Workflow for Cance...
A Ready-to-Analyze High-Plex Spatial Signature Development Workflow for Cance...InsideScientific
 
Molecule Transport across Cell Membranes: Electrochemical Quantification at t...
Molecule Transport across Cell Membranes: Electrochemical Quantification at t...Molecule Transport across Cell Membranes: Electrochemical Quantification at t...
Molecule Transport across Cell Membranes: Electrochemical Quantification at t...InsideScientific
 
Exploring Estrogen’s Role in Metabolism and the Use of 13C-Labeled Nutrients ...
Exploring Estrogen’s Role in Metabolism and the Use of 13C-Labeled Nutrients ...Exploring Estrogen’s Role in Metabolism and the Use of 13C-Labeled Nutrients ...
Exploring Estrogen’s Role in Metabolism and the Use of 13C-Labeled Nutrients ...InsideScientific
 
Longitudinal Plasma Samples: Paving the Way for Precision Oncology
Longitudinal Plasma Samples: Paving the Way for Precision OncologyLongitudinal Plasma Samples: Paving the Way for Precision Oncology
Longitudinal Plasma Samples: Paving the Way for Precision OncologyInsideScientific
 
Fully Characterized, Standardized Human Induced Pluripotent Stem Cell Line an...
Fully Characterized, Standardized Human Induced Pluripotent Stem Cell Line an...Fully Characterized, Standardized Human Induced Pluripotent Stem Cell Line an...
Fully Characterized, Standardized Human Induced Pluripotent Stem Cell Line an...InsideScientific
 
How to Create CRISPR-Edited T Cells More Efficiently for Tomorrow's Cell Ther...
How to Create CRISPR-Edited T Cells More Efficiently for Tomorrow's Cell Ther...How to Create CRISPR-Edited T Cells More Efficiently for Tomorrow's Cell Ther...
How to Create CRISPR-Edited T Cells More Efficiently for Tomorrow's Cell Ther...InsideScientific
 
Peripheral and Cerebral Vascular Responses Following High-Intensity Interval ...
Peripheral and Cerebral Vascular Responses Following High-Intensity Interval ...Peripheral and Cerebral Vascular Responses Following High-Intensity Interval ...
Peripheral and Cerebral Vascular Responses Following High-Intensity Interval ...InsideScientific
 
Leveraging Programmable CRISPR-Associated Transposases for Next-Generation Ge...
Leveraging Programmable CRISPR-Associated Transposases for Next-Generation Ge...Leveraging Programmable CRISPR-Associated Transposases for Next-Generation Ge...
Leveraging Programmable CRISPR-Associated Transposases for Next-Generation Ge...InsideScientific
 
Simple Tips to Significantly Improve Rodent Surgical Outcomes
 Simple Tips to Significantly Improve Rodent Surgical Outcomes Simple Tips to Significantly Improve Rodent Surgical Outcomes
Simple Tips to Significantly Improve Rodent Surgical OutcomesInsideScientific
 
Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...
Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...
Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...InsideScientific
 
Creating Better Gene-Edited Cell Lines with the FAST-HDR System
Creating Better Gene-Edited Cell Lines with the FAST-HDR SystemCreating Better Gene-Edited Cell Lines with the FAST-HDR System
Creating Better Gene-Edited Cell Lines with the FAST-HDR SystemInsideScientific
 
Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...
Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...
Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...InsideScientific
 
Designing Causal Inference Studies Using Real-World Data
Designing Causal Inference Studies Using Real-World DataDesigning Causal Inference Studies Using Real-World Data
Designing Causal Inference Studies Using Real-World DataInsideScientific
 
Social Media Data: Opportunities and Insights for Clinical Research
Social Media Data: Opportunities and Insights for Clinical ResearchSocial Media Data: Opportunities and Insights for Clinical Research
Social Media Data: Opportunities and Insights for Clinical ResearchInsideScientific
 
We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...
We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...
We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...InsideScientific
 
Antibody Discovery by Single B Cell Screening on Beacon®
Antibody Discovery by Single B Cell Screening on Beacon®Antibody Discovery by Single B Cell Screening on Beacon®
Antibody Discovery by Single B Cell Screening on Beacon®InsideScientific
 
Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...
Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...
Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...InsideScientific
 
Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...
Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...
Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...InsideScientific
 
Cardiometabolic Disease Pathophysiology & Novel Therapies for Atherosclerosis...
Cardiometabolic Disease Pathophysiology & Novel Therapies for Atherosclerosis...Cardiometabolic Disease Pathophysiology & Novel Therapies for Atherosclerosis...
Cardiometabolic Disease Pathophysiology & Novel Therapies for Atherosclerosis...InsideScientific
 

More from InsideScientific (20)

Next-Generation Safety Assessment Tools for Advancing In Vivo to In Vitro Tra...
Next-Generation Safety Assessment Tools for Advancing In Vivo to In Vitro Tra...Next-Generation Safety Assessment Tools for Advancing In Vivo to In Vitro Tra...
Next-Generation Safety Assessment Tools for Advancing In Vivo to In Vitro Tra...
 
A Ready-to-Analyze High-Plex Spatial Signature Development Workflow for Cance...
A Ready-to-Analyze High-Plex Spatial Signature Development Workflow for Cance...A Ready-to-Analyze High-Plex Spatial Signature Development Workflow for Cance...
A Ready-to-Analyze High-Plex Spatial Signature Development Workflow for Cance...
 
Molecule Transport across Cell Membranes: Electrochemical Quantification at t...
Molecule Transport across Cell Membranes: Electrochemical Quantification at t...Molecule Transport across Cell Membranes: Electrochemical Quantification at t...
Molecule Transport across Cell Membranes: Electrochemical Quantification at t...
 
Exploring Estrogen’s Role in Metabolism and the Use of 13C-Labeled Nutrients ...
Exploring Estrogen’s Role in Metabolism and the Use of 13C-Labeled Nutrients ...Exploring Estrogen’s Role in Metabolism and the Use of 13C-Labeled Nutrients ...
Exploring Estrogen’s Role in Metabolism and the Use of 13C-Labeled Nutrients ...
 
Longitudinal Plasma Samples: Paving the Way for Precision Oncology
Longitudinal Plasma Samples: Paving the Way for Precision OncologyLongitudinal Plasma Samples: Paving the Way for Precision Oncology
Longitudinal Plasma Samples: Paving the Way for Precision Oncology
 
Fully Characterized, Standardized Human Induced Pluripotent Stem Cell Line an...
Fully Characterized, Standardized Human Induced Pluripotent Stem Cell Line an...Fully Characterized, Standardized Human Induced Pluripotent Stem Cell Line an...
Fully Characterized, Standardized Human Induced Pluripotent Stem Cell Line an...
 
How to Create CRISPR-Edited T Cells More Efficiently for Tomorrow's Cell Ther...
How to Create CRISPR-Edited T Cells More Efficiently for Tomorrow's Cell Ther...How to Create CRISPR-Edited T Cells More Efficiently for Tomorrow's Cell Ther...
How to Create CRISPR-Edited T Cells More Efficiently for Tomorrow's Cell Ther...
 
Peripheral and Cerebral Vascular Responses Following High-Intensity Interval ...
Peripheral and Cerebral Vascular Responses Following High-Intensity Interval ...Peripheral and Cerebral Vascular Responses Following High-Intensity Interval ...
Peripheral and Cerebral Vascular Responses Following High-Intensity Interval ...
 
Leveraging Programmable CRISPR-Associated Transposases for Next-Generation Ge...
Leveraging Programmable CRISPR-Associated Transposases for Next-Generation Ge...Leveraging Programmable CRISPR-Associated Transposases for Next-Generation Ge...
Leveraging Programmable CRISPR-Associated Transposases for Next-Generation Ge...
 
Simple Tips to Significantly Improve Rodent Surgical Outcomes
 Simple Tips to Significantly Improve Rodent Surgical Outcomes Simple Tips to Significantly Improve Rodent Surgical Outcomes
Simple Tips to Significantly Improve Rodent Surgical Outcomes
 
Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...
Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...
Cardiovascular Autonomic Dysfunction in the Post-COVID Landscape: Detection a...
 
Creating Better Gene-Edited Cell Lines with the FAST-HDR System
Creating Better Gene-Edited Cell Lines with the FAST-HDR SystemCreating Better Gene-Edited Cell Lines with the FAST-HDR System
Creating Better Gene-Edited Cell Lines with the FAST-HDR System
 
Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...
Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...
Functional Recovery of the Musculoskeletal System Following Injury - Leveragi...
 
Designing Causal Inference Studies Using Real-World Data
Designing Causal Inference Studies Using Real-World DataDesigning Causal Inference Studies Using Real-World Data
Designing Causal Inference Studies Using Real-World Data
 
Social Media Data: Opportunities and Insights for Clinical Research
Social Media Data: Opportunities and Insights for Clinical ResearchSocial Media Data: Opportunities and Insights for Clinical Research
Social Media Data: Opportunities and Insights for Clinical Research
 
We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...
We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...
We Are More Than What We Eat Dietary Interventions Depend on Sex and Genetic ...
 
Antibody Discovery by Single B Cell Screening on Beacon®
Antibody Discovery by Single B Cell Screening on Beacon®Antibody Discovery by Single B Cell Screening on Beacon®
Antibody Discovery by Single B Cell Screening on Beacon®
 
Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...
Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...
Experimental Design Considerations to Optimize Chronic Cardiovascular Telemet...
 
Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...
Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...
Strategic Approaches to Age-Related Metabolic Insufficiency and Transition in...
 
Cardiometabolic Disease Pathophysiology & Novel Therapies for Atherosclerosis...
Cardiometabolic Disease Pathophysiology & Novel Therapies for Atherosclerosis...Cardiometabolic Disease Pathophysiology & Novel Therapies for Atherosclerosis...
Cardiometabolic Disease Pathophysiology & Novel Therapies for Atherosclerosis...
 

Recently uploaded

CALL ON ➥8923113531 🔝Call Girls Kesar Bagh Lucknow best Night Fun service 🪡
CALL ON ➥8923113531 🔝Call Girls Kesar Bagh Lucknow best Night Fun service  🪡CALL ON ➥8923113531 🔝Call Girls Kesar Bagh Lucknow best Night Fun service  🪡
CALL ON ➥8923113531 🔝Call Girls Kesar Bagh Lucknow best Night Fun service 🪡anilsa9823
 
Bentham & Hooker's Classification. along with the merits and demerits of the ...
Bentham & Hooker's Classification. along with the merits and demerits of the ...Bentham & Hooker's Classification. along with the merits and demerits of the ...
Bentham & Hooker's Classification. along with the merits and demerits of the ...Nistarini College, Purulia (W.B) India
 
SOLUBLE PATTERN RECOGNITION RECEPTORS.pptx
SOLUBLE PATTERN RECOGNITION RECEPTORS.pptxSOLUBLE PATTERN RECOGNITION RECEPTORS.pptx
SOLUBLE PATTERN RECOGNITION RECEPTORS.pptxkessiyaTpeter
 
Hubble Asteroid Hunter III. Physical properties of newly found asteroids
Hubble Asteroid Hunter III. Physical properties of newly found asteroidsHubble Asteroid Hunter III. Physical properties of newly found asteroids
Hubble Asteroid Hunter III. Physical properties of newly found asteroidsSérgio Sacani
 
All-domain Anomaly Resolution Office U.S. Department of Defense (U) Case: “Eg...
All-domain Anomaly Resolution Office U.S. Department of Defense (U) Case: “Eg...All-domain Anomaly Resolution Office U.S. Department of Defense (U) Case: “Eg...
All-domain Anomaly Resolution Office U.S. Department of Defense (U) Case: “Eg...Sérgio Sacani
 
Call Girls in Munirka Delhi 💯Call Us 🔝8264348440🔝
Call Girls in Munirka Delhi 💯Call Us 🔝8264348440🔝Call Girls in Munirka Delhi 💯Call Us 🔝8264348440🔝
Call Girls in Munirka Delhi 💯Call Us 🔝8264348440🔝soniya singh
 
Module 4: Mendelian Genetics and Punnett Square
Module 4:  Mendelian Genetics and Punnett SquareModule 4:  Mendelian Genetics and Punnett Square
Module 4: Mendelian Genetics and Punnett SquareIsiahStephanRadaza
 
Boyles law module in the grade 10 science
Boyles law module in the grade 10 scienceBoyles law module in the grade 10 science
Boyles law module in the grade 10 sciencefloriejanemacaya1
 
STERILITY TESTING OF PHARMACEUTICALS ppt by DR.C.P.PRINCE
STERILITY TESTING OF PHARMACEUTICALS ppt by DR.C.P.PRINCESTERILITY TESTING OF PHARMACEUTICALS ppt by DR.C.P.PRINCE
STERILITY TESTING OF PHARMACEUTICALS ppt by DR.C.P.PRINCEPRINCE C P
 
Physiochemical properties of nanomaterials and its nanotoxicity.pptx
Physiochemical properties of nanomaterials and its nanotoxicity.pptxPhysiochemical properties of nanomaterials and its nanotoxicity.pptx
Physiochemical properties of nanomaterials and its nanotoxicity.pptxAArockiyaNisha
 
Grafana in space: Monitoring Japan's SLIM moon lander in real time
Grafana in space: Monitoring Japan's SLIM moon lander  in real timeGrafana in space: Monitoring Japan's SLIM moon lander  in real time
Grafana in space: Monitoring Japan's SLIM moon lander in real timeSatoshi NAKAHIRA
 
A relative description on Sonoporation.pdf
A relative description on Sonoporation.pdfA relative description on Sonoporation.pdf
A relative description on Sonoporation.pdfnehabiju2046
 
Animal Communication- Auditory and Visual.pptx
Animal Communication- Auditory and Visual.pptxAnimal Communication- Auditory and Visual.pptx
Animal Communication- Auditory and Visual.pptxUmerFayaz5
 
Lucknow 💋 Russian Call Girls Lucknow Finest Escorts Service 8923113531 Availa...
Lucknow 💋 Russian Call Girls Lucknow Finest Escorts Service 8923113531 Availa...Lucknow 💋 Russian Call Girls Lucknow Finest Escorts Service 8923113531 Availa...
Lucknow 💋 Russian Call Girls Lucknow Finest Escorts Service 8923113531 Availa...anilsa9823
 
Artificial Intelligence In Microbiology by Dr. Prince C P
Artificial Intelligence In Microbiology by Dr. Prince C PArtificial Intelligence In Microbiology by Dr. Prince C P
Artificial Intelligence In Microbiology by Dr. Prince C PPRINCE C P
 
Is RISC-V ready for HPC workload? Maybe?
Is RISC-V ready for HPC workload? Maybe?Is RISC-V ready for HPC workload? Maybe?
Is RISC-V ready for HPC workload? Maybe?Patrick Diehl
 
Biopesticide (2).pptx .This slides helps to know the different types of biop...
Biopesticide (2).pptx  .This slides helps to know the different types of biop...Biopesticide (2).pptx  .This slides helps to know the different types of biop...
Biopesticide (2).pptx .This slides helps to know the different types of biop...RohitNehra6
 
Dashanga agada a formulation of Agada tantra dealt in 3 Rd year bams agada tanta
Dashanga agada a formulation of Agada tantra dealt in 3 Rd year bams agada tantaDashanga agada a formulation of Agada tantra dealt in 3 Rd year bams agada tanta
Dashanga agada a formulation of Agada tantra dealt in 3 Rd year bams agada tantaPraksha3
 
Nanoparticles synthesis and characterization​ ​
Nanoparticles synthesis and characterization​  ​Nanoparticles synthesis and characterization​  ​
Nanoparticles synthesis and characterization​ ​kaibalyasahoo82800
 

Recently uploaded (20)

CALL ON ➥8923113531 🔝Call Girls Kesar Bagh Lucknow best Night Fun service 🪡
CALL ON ➥8923113531 🔝Call Girls Kesar Bagh Lucknow best Night Fun service  🪡CALL ON ➥8923113531 🔝Call Girls Kesar Bagh Lucknow best Night Fun service  🪡
CALL ON ➥8923113531 🔝Call Girls Kesar Bagh Lucknow best Night Fun service 🪡
 
Bentham & Hooker's Classification. along with the merits and demerits of the ...
Bentham & Hooker's Classification. along with the merits and demerits of the ...Bentham & Hooker's Classification. along with the merits and demerits of the ...
Bentham & Hooker's Classification. along with the merits and demerits of the ...
 
SOLUBLE PATTERN RECOGNITION RECEPTORS.pptx
SOLUBLE PATTERN RECOGNITION RECEPTORS.pptxSOLUBLE PATTERN RECOGNITION RECEPTORS.pptx
SOLUBLE PATTERN RECOGNITION RECEPTORS.pptx
 
Hubble Asteroid Hunter III. Physical properties of newly found asteroids
Hubble Asteroid Hunter III. Physical properties of newly found asteroidsHubble Asteroid Hunter III. Physical properties of newly found asteroids
Hubble Asteroid Hunter III. Physical properties of newly found asteroids
 
All-domain Anomaly Resolution Office U.S. Department of Defense (U) Case: “Eg...
All-domain Anomaly Resolution Office U.S. Department of Defense (U) Case: “Eg...All-domain Anomaly Resolution Office U.S. Department of Defense (U) Case: “Eg...
All-domain Anomaly Resolution Office U.S. Department of Defense (U) Case: “Eg...
 
Call Girls in Munirka Delhi 💯Call Us 🔝8264348440🔝
Call Girls in Munirka Delhi 💯Call Us 🔝8264348440🔝Call Girls in Munirka Delhi 💯Call Us 🔝8264348440🔝
Call Girls in Munirka Delhi 💯Call Us 🔝8264348440🔝
 
Module 4: Mendelian Genetics and Punnett Square
Module 4:  Mendelian Genetics and Punnett SquareModule 4:  Mendelian Genetics and Punnett Square
Module 4: Mendelian Genetics and Punnett Square
 
Boyles law module in the grade 10 science
Boyles law module in the grade 10 scienceBoyles law module in the grade 10 science
Boyles law module in the grade 10 science
 
STERILITY TESTING OF PHARMACEUTICALS ppt by DR.C.P.PRINCE
STERILITY TESTING OF PHARMACEUTICALS ppt by DR.C.P.PRINCESTERILITY TESTING OF PHARMACEUTICALS ppt by DR.C.P.PRINCE
STERILITY TESTING OF PHARMACEUTICALS ppt by DR.C.P.PRINCE
 
Physiochemical properties of nanomaterials and its nanotoxicity.pptx
Physiochemical properties of nanomaterials and its nanotoxicity.pptxPhysiochemical properties of nanomaterials and its nanotoxicity.pptx
Physiochemical properties of nanomaterials and its nanotoxicity.pptx
 
Grafana in space: Monitoring Japan's SLIM moon lander in real time
Grafana in space: Monitoring Japan's SLIM moon lander  in real timeGrafana in space: Monitoring Japan's SLIM moon lander  in real time
Grafana in space: Monitoring Japan's SLIM moon lander in real time
 
A relative description on Sonoporation.pdf
A relative description on Sonoporation.pdfA relative description on Sonoporation.pdf
A relative description on Sonoporation.pdf
 
Animal Communication- Auditory and Visual.pptx
Animal Communication- Auditory and Visual.pptxAnimal Communication- Auditory and Visual.pptx
Animal Communication- Auditory and Visual.pptx
 
Lucknow 💋 Russian Call Girls Lucknow Finest Escorts Service 8923113531 Availa...
Lucknow 💋 Russian Call Girls Lucknow Finest Escorts Service 8923113531 Availa...Lucknow 💋 Russian Call Girls Lucknow Finest Escorts Service 8923113531 Availa...
Lucknow 💋 Russian Call Girls Lucknow Finest Escorts Service 8923113531 Availa...
 
Artificial Intelligence In Microbiology by Dr. Prince C P
Artificial Intelligence In Microbiology by Dr. Prince C PArtificial Intelligence In Microbiology by Dr. Prince C P
Artificial Intelligence In Microbiology by Dr. Prince C P
 
Engler and Prantl system of classification in plant taxonomy
Engler and Prantl system of classification in plant taxonomyEngler and Prantl system of classification in plant taxonomy
Engler and Prantl system of classification in plant taxonomy
 
Is RISC-V ready for HPC workload? Maybe?
Is RISC-V ready for HPC workload? Maybe?Is RISC-V ready for HPC workload? Maybe?
Is RISC-V ready for HPC workload? Maybe?
 
Biopesticide (2).pptx .This slides helps to know the different types of biop...
Biopesticide (2).pptx  .This slides helps to know the different types of biop...Biopesticide (2).pptx  .This slides helps to know the different types of biop...
Biopesticide (2).pptx .This slides helps to know the different types of biop...
 
Dashanga agada a formulation of Agada tantra dealt in 3 Rd year bams agada tanta
Dashanga agada a formulation of Agada tantra dealt in 3 Rd year bams agada tantaDashanga agada a formulation of Agada tantra dealt in 3 Rd year bams agada tanta
Dashanga agada a formulation of Agada tantra dealt in 3 Rd year bams agada tanta
 
Nanoparticles synthesis and characterization​ ​
Nanoparticles synthesis and characterization​  ​Nanoparticles synthesis and characterization​  ​
Nanoparticles synthesis and characterization​ ​
 

Exploring Predictive Biomarkers and ERK1/2 Phosphorylation: A New Horizon in Forecasting Survival and Response to Immune Checkpoint Blockade in Glioblastoma Treatment

  • 1.
  • 2. Víctor Andrés Arrieta González MD,PhD Exploring Predictive Biomarkers and ERK1/2 Phosphorylation: A New Horizon in Forecasting Survival and Response to Immune Checkpoint Blockade in Glioblastoma Treatment
  • 3.
  • 4. Clinical GBM responder and non-responder to PD-1 blockade 49.4 0.11 16.7 33.8 0 10 3 10 4 CD4 APC-Cy7 0 10 3 10 4 CD8 PE-Cy7-A 74.2 0.54 18.4 6.91 0 10 3 10 4 Comp-APC-Cy7-A 0 10 3 10 4 Comp-PE-Cy7-A 38.4 0.12 56.8 4.72 0 10 3 10 4 CD4 APC-Cy7 0 10 3 10 4 CD8 PE-Cy7 Start of anti-PD-1 therapy Start of anti-PD-1 therapy Last seen alive 21 months after PD-1 blockade 2 weeks 10 months 11 months 13 months 15 months Resection Resection Resection 2 months Death 6 months after PD-1 blockade Recurrence Recurrence Responder Non-responder CD3 Blood Resected tissue CSF 200 µm Arrieta VA, Chen AX, et al, Nat Cancer 2021
  • 5. Enrichment of BRAF/PTPN11 mutations in responder patients Zhao J et al, Nat Med 2019 MAPK pathway Pratilas CA et al, Clin Cancer Res 2010 PTPN11
  • 6. p-ERK is associated with longer survival in recurrent GBM patients treated with anti-PD-1 therapy 250 µm 250 µm High p-ERK Low p-ERK Arrieta VA, Chen AX, et al, Nat Cancer 2021
  • 7. Patients with longer overall survival exhibited high levels of p-ERK regardless of the genetic status of the BRAF/PTPN11 Arrieta VA, Chen AX, et al, Nat Cancer 2021
  • 8. Cloughesy TF et al, Nat Med 2019 p-ERK is associated with overall survival in an independent cohort of recurrent GBM patients treated with adjuvant PD-1 blockade Arrieta VA, Chen AX, et al, Nat Cancer 2021
  • 9. p-ERK is predominantly expressed by GBM cells p-ERK IHC H&E p-ERK IHC H&E p-ERK IHC H&E BRAFV600E mutant GBM High p-ERK Wild-type BRAF GBM High p-ERK Wild-type BRAF GBM Low p-ERK 200 µm 200 µm 200 µm 200 µm 200 µm 200 µm p-ERK SOX2 DAPI CD163 DAPI SOX2 TMEM119 p-ERK SOX2 DAPI CD163 DAPI SOX2 TMEM119 p-ERK SOX2 DAPI CD163 DAPI SOX2 TMEM119 Arrieta VA, Chen AX, et al, Nat Cancer 2021
  • 10. High-p-ERK GBMs contain abundant TMEM119+ microglia p-ERK Iba1 250 µm 250 µm Arrieta VA, Chen AX, et al, Nat Cancer 2021
  • 11. TMEM119+ microglia are closer to SOX2+ p-ERK+ cells TMEM119+ cells CD163+ cells SOX2+ p-ERK+ cells Mean distance to the nearest neighbor From To SOX2+ p-ERK- cells TMEM119+ SOX2+ p-ERK+ TMEM119+ SOX2+ p-ERK+ High p-ERK Low p-ERK 200 µm 200 µm Arrieta VA, Chen AX, et al, Nat Cancer 2021
  • 12. CD163+ cells GFAP+ p-ERK- cells Mean distance to the nearest neighbor From To GFAP+ p-ERK+ cells Arrieta VA, Chen AX, et al, Nat Cancer 2021 CD163+ GFAP+ pERK+ CD163+ GFAP+ pERK+ High p-ERK Low p-ERK 200 µm 200 µm CD163+ myeloid cells are closer to GFAP+ p-ERK+ cells
  • 13. Analysis of GBM-infiltrating microglia and macrophages by single-cell RNA-seq Arrieta VA, Chen AX, et al, Nat Cancer 2021
  • 14. Myeloid cells from high p-ERK GBMs have increased MHC II expression Arrieta VA, Chen AX, et al, Nat Cancer 2021 GO MHC Class II protein Complex Binding 1.75 1.50 1.25 1.00 0.00 0.75 0.50 0.25 GO MHC Class II protein Complex Binding 0.8 0.6 0.4 0.2 0.0 1.0 0.5 0.0 -0.5 0 5000 10000 15000 20000 25000 High p-ERK Low p-ERK
  • 15. Myeloid cells from high p-ERK GBMs have increased MHC II expression Arrieta VA, Chen AX, et al, Nat Cancer 2021
  • 16. • ERK1/2 phosphorylation shows that is a predictive biomarker of immune checkpoint blockade including anti-PD-1 therapy in three independent cohorts of recurrent GBM patients. • GBMs that exhibit high numbers of p-ERK+ cells contain abundant TMEM119+ microglia. • Myeloid cells derived from high p-ERK GBMs exhibit increased MHC class II expression compared to myeloid cells derived from low p-ERK GBMs. Conclusions
  • 17. • There are several aspects to consider before implementing p-ERK as a biomarker for response to anti-PD-1 therapy: • Further validation in additional clinical cohorts • Cut point value optimization • Alternative techniques for MAPK pathway activation • Standardized protocols for p-ERK assessment Considerations
  • 18. Acknowledgments Columbia University • Junfei Zhao • David Cieremans • Pavan Upadhyayula • Jinzhou Yuan • Wenting Zhao • Brice Laffleur • Uttiya Basu • Gerson Rothschild • Peter Sims • Peter Canoll • Jeffrey N. Bruce Northwestern University • Seong Jae Kang • Kirsten B. Burdett • Crismita Dmello • Andrew Gould • Matthew McCord • Li Chen • Daniel Zhang • Dinesh Jaishankar • Joseph Shilati • Christina Amidei • Lee D Cooper • Rimas V. Lukas • Hui Zhang • Jonathan T. Yamaguchi • Daniel J. Brat • Bin Zhang • Roger Stupp MD Anderson Cancer Center • Cynthia Kassab • Xiaoyang Ling • Jared K. Burks UCLA • Robert Prins • Tim F. Cloughesy Andrew X. Chen J. Robert Kane Adam Sonabend Fabio M. Iwamoto Raul Rabadan Amy Heimberger Craig Horbinski Catalina Lee Chang