Imperial College London
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Dr Alessio Cortellini MD PhD

Faculty of Medicine, Department of Surgery & Cancer

Honorary Clinical Lecturer
 
 
 
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Contact

 

a.cortellini

 
 
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Location

 

138ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Naqash:2023:10.1136/jitc-2023-007310,
author = {Naqash, AR and McCallen, JD and Mi, E and Iivanainen, S and Marie, MA and Gramenitskaya, D and Clark, J and Koivunen, JP and Macherla, S and Jonnalagadda, S and Polsani, S and Jiwani, RA and Hafiz, M and Muzaffar, M and Brunetti, L and Stroud, CRG and Walker, PR and Wang, K and Chung, Y and Ruppin, E and Lee, S-H and Yang, LV and Pinato, DJ and Lee, JS and Cortellini, A},
doi = {10.1136/jitc-2023-007310},
journal = {J Immunother Cancer},
title = {Increased interleukin-6/C-reactive protein levels are associated with the upregulation of the adenosine pathway and serve as potential markers of therapeutic resistance to immune checkpoint inhibitor-based therapies in non-small cell lung cancer.},
url = {http://dx.doi.org/10.1136/jitc-2023-007310},
volume = {11},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Systemic immune activation, hallmarked by C-reactive protein (CRP) and interleukin-6 (IL-6), can modulate antitumor immune responses. In this study, we evaluated the role of IL-6 and CRP in the stratification of patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). We also interrogated the underlying immunosuppressive mechanisms driven by the IL-6/CRP axis. METHODS: In cohort A (n=308), we estimated the association of baseline CRP with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in patients with NSCLC treated with ICIs alone or with chemo-immunotherapy (Chemo-ICI). Baseline tumor bulk RNA sequencing (RNA-seq) of lung adenocarcinomas (LUADs) treated with pembrolizumab (cohort B, n=59) was used to evaluate differential expression of purine metabolism, as well as correlate IL-6 expression with PFS. CODEFACS approach was applied to deconvolve cohort B to characterize the tumor microenvironment by reconstructing the cell-type-specific transcriptome from bulk expression. Using the LUAD cohort from The Cancer Genome Atlas (TCGA) we explored the correlation between IL-6 expression and adenosine gene signatures. In a third cohort (cohort C, n=18), plasma concentrations of CRP, adenosine 2a receptor (A2aR), and IL-6 were measured using ELISA. RESULTS: In cohort A, 67.2% of patients had a baseline CRP≥10 mg/L (CRP-H). Patients with CRP-H achieved shorter OS (8.6 vs 14.8 months; p=0.006), shorter PFS (3.3 vs 6.6 months; p=0.013), and lower ORR (24.7% vs 46.3%; p=0.015). After adjusting for relevant clinical variables, CRP-H was confirmed as an independent predictor of increased risk of death (HR 1.51, 95% CI: 1.09 to 2.11) and lower probability of achieving disease response (OR 0.34, 95% CI: 0.13 to 0.89). In cohort B, RNA-seq analysis demonstrated higher IL-6 expression on tumor cells of non-responders, along with a shorter PFS (p<0.05) and enrichment of the puri
AU  - Naqash,AR
AU  - McCallen,JD
AU  - Mi,E
AU  - Iivanainen,S
AU  - Marie,MA
AU  - Gramenitskaya,D
AU  - Clark,J
AU  - Koivunen,JP
AU  - Macherla,S
AU  - Jonnalagadda,S
AU  - Polsani,S
AU  - Jiwani,RA
AU  - Hafiz,M
AU  - Muzaffar,M
AU  - Brunetti,L
AU  - Stroud,CRG
AU  - Walker,PR
AU  - Wang,K
AU  - Chung,Y
AU  - Ruppin,E
AU  - Lee,S-H
AU  - Yang,LV
AU  - Pinato,DJ
AU  - Lee,JS
AU  - Cortellini,A
DO  - 10.1136/jitc-2023-007310
PY  - 2023///
TI  - Increased interleukin-6/C-reactive protein levels are associated with the upregulation of the adenosine pathway and serve as potential markers of therapeutic resistance to immune checkpoint inhibitor-based therapies in non-small cell lung cancer.
T2  - J Immunother Cancer
UR  - http://dx.doi.org/10.1136/jitc-2023-007310
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37852738
VL  - 11
ER  -
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