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Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer

BACKGROUND: Anti-PD-1 and PD-L1 antibodies (mAbs) are approved immunotherapy agents to treat metastatic non-small cell lung cancer (NSCLC) patients. Only a minority of patients responds to these treatments and biomarkers predicting response are currently lacking. METHODS: Immunoscore-Immune-Checkpoi...

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Autores principales: Ghiringhelli, François, Bibeau, Frederic, Greillier, Laurent, Fumet, Jean-David, Ilie, Alis, Monville, Florence, Laugé, Caroline, Catteau, Aurélie, Boquet, Isabelle, Majdi, Amine, Morgand, Erwan, Oulkhouir, Youssef, Brandone, Nicolas, Adam, Julien, Sbarrato, Thomas, Kassambara, Alboukadel, Fieschi, Jacques, Garcia, Stéphane, Lepage, Anne Laure, Tomasini, Pascale, Galon, Jérôme
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232659/
https://www.ncbi.nlm.nih.gov/pubmed/37244159
http://dx.doi.org/10.1016/j.ebiom.2023.104633
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author Ghiringhelli, François
Bibeau, Frederic
Greillier, Laurent
Fumet, Jean-David
Ilie, Alis
Monville, Florence
Laugé, Caroline
Catteau, Aurélie
Boquet, Isabelle
Majdi, Amine
Morgand, Erwan
Oulkhouir, Youssef
Brandone, Nicolas
Adam, Julien
Sbarrato, Thomas
Kassambara, Alboukadel
Fieschi, Jacques
Garcia, Stéphane
Lepage, Anne Laure
Tomasini, Pascale
Galon, Jérôme
author_facet Ghiringhelli, François
Bibeau, Frederic
Greillier, Laurent
Fumet, Jean-David
Ilie, Alis
Monville, Florence
Laugé, Caroline
Catteau, Aurélie
Boquet, Isabelle
Majdi, Amine
Morgand, Erwan
Oulkhouir, Youssef
Brandone, Nicolas
Adam, Julien
Sbarrato, Thomas
Kassambara, Alboukadel
Fieschi, Jacques
Garcia, Stéphane
Lepage, Anne Laure
Tomasini, Pascale
Galon, Jérôme
author_sort Ghiringhelli, François
collection PubMed
description BACKGROUND: Anti-PD-1 and PD-L1 antibodies (mAbs) are approved immunotherapy agents to treat metastatic non-small cell lung cancer (NSCLC) patients. Only a minority of patients responds to these treatments and biomarkers predicting response are currently lacking. METHODS: Immunoscore-Immune-Checkpoint (Immunoscore-IC), an in vitro diagnostic test, was used on 471 routine single FFPE-slides, and the duplex-immunohistochemistry CD8 and PD-L1 staining was quantified using digital-pathology. Analytical validation was performed on two independent cohorts of 206 NSCLC patients. Quantitative parameters related to cell location, number, proximity and clustering were analysed. The Immunoscore-IC was applied on a first cohort of metastatic NSCLC patients (n = 133), treated with anti-PD1 or anti-PD-L1 mAbs. Another independent cohort (n = 132) served as validation. FINDINGS: Anti-PDL1 clone (HDX3) has similar characteristics as anti-PD-L1 clones (22C3, SP263). Densities of PD-L1+ cells, CD8+ cells and distances between CD8+ and PD-L1+ cells were quantified and the Immunoscore-IC classification was computed. Using univariate Cox model, 5 histological dichotomised variables (CD8 free of PD-L1+ cells, CD8 clusters, CD8 cells in proximity of PD-L1 cells, CD8 density and PD-L1 cells in proximity of CD8 cells) were significantly associated with Progression-Free Survival (PFS) (all P < 0.0001). Immunoscore-IC classification improved the discriminating power of prognostic model, which included clinical variables and pathologist PD-L1 assessment. In two categories, the Immunoscore-IC risk-score was significantly associated with patients’ PFS (HR = 0.39, 95% CI (0.26–0.59), P < 0.0001) and Overall Survival (OS) (HR = 0.42, 95% CI (0.27–0.65), P < 0.0001) in the training-set. Further increased hazard ratios (HR) were found when stratifying patients into three-category Immunoscore-IC (IS-IC). All patients with Low-IS-IC progressed in less than 18 months, whereas PFS at 36 months were 34% and 33% of High-IS-IC patients in the training and validation sets, respectively. INTERPRETATION: Immunoscore-IC is a powerful tool to predict the efficacy of immune-checkpoint inhibitors (ICIs) in patients with NSCLC. FUNDING: 10.13039/100018771Veracyte, 10.13039/501100001677INSERM, 10.13039/501100018872Labex Immuno-Oncology, Transcan ERAnet European project, 10.13039/100007391ARC, SIRIC, CARPEM, 10.13039/501100004099Ligue Contre le Cancer, ANR, 10.13039/100008982QNRF, 10.13039/501100006364INCa France, Louis Jeantet Prize Foundation.
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spelling pubmed-102326592023-06-02 Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer Ghiringhelli, François Bibeau, Frederic Greillier, Laurent Fumet, Jean-David Ilie, Alis Monville, Florence Laugé, Caroline Catteau, Aurélie Boquet, Isabelle Majdi, Amine Morgand, Erwan Oulkhouir, Youssef Brandone, Nicolas Adam, Julien Sbarrato, Thomas Kassambara, Alboukadel Fieschi, Jacques Garcia, Stéphane Lepage, Anne Laure Tomasini, Pascale Galon, Jérôme eBioMedicine Articles BACKGROUND: Anti-PD-1 and PD-L1 antibodies (mAbs) are approved immunotherapy agents to treat metastatic non-small cell lung cancer (NSCLC) patients. Only a minority of patients responds to these treatments and biomarkers predicting response are currently lacking. METHODS: Immunoscore-Immune-Checkpoint (Immunoscore-IC), an in vitro diagnostic test, was used on 471 routine single FFPE-slides, and the duplex-immunohistochemistry CD8 and PD-L1 staining was quantified using digital-pathology. Analytical validation was performed on two independent cohorts of 206 NSCLC patients. Quantitative parameters related to cell location, number, proximity and clustering were analysed. The Immunoscore-IC was applied on a first cohort of metastatic NSCLC patients (n = 133), treated with anti-PD1 or anti-PD-L1 mAbs. Another independent cohort (n = 132) served as validation. FINDINGS: Anti-PDL1 clone (HDX3) has similar characteristics as anti-PD-L1 clones (22C3, SP263). Densities of PD-L1+ cells, CD8+ cells and distances between CD8+ and PD-L1+ cells were quantified and the Immunoscore-IC classification was computed. Using univariate Cox model, 5 histological dichotomised variables (CD8 free of PD-L1+ cells, CD8 clusters, CD8 cells in proximity of PD-L1 cells, CD8 density and PD-L1 cells in proximity of CD8 cells) were significantly associated with Progression-Free Survival (PFS) (all P < 0.0001). Immunoscore-IC classification improved the discriminating power of prognostic model, which included clinical variables and pathologist PD-L1 assessment. In two categories, the Immunoscore-IC risk-score was significantly associated with patients’ PFS (HR = 0.39, 95% CI (0.26–0.59), P < 0.0001) and Overall Survival (OS) (HR = 0.42, 95% CI (0.27–0.65), P < 0.0001) in the training-set. Further increased hazard ratios (HR) were found when stratifying patients into three-category Immunoscore-IC (IS-IC). All patients with Low-IS-IC progressed in less than 18 months, whereas PFS at 36 months were 34% and 33% of High-IS-IC patients in the training and validation sets, respectively. INTERPRETATION: Immunoscore-IC is a powerful tool to predict the efficacy of immune-checkpoint inhibitors (ICIs) in patients with NSCLC. FUNDING: 10.13039/100018771Veracyte, 10.13039/501100001677INSERM, 10.13039/501100018872Labex Immuno-Oncology, Transcan ERAnet European project, 10.13039/100007391ARC, SIRIC, CARPEM, 10.13039/501100004099Ligue Contre le Cancer, ANR, 10.13039/100008982QNRF, 10.13039/501100006364INCa France, Louis Jeantet Prize Foundation. Elsevier 2023-05-25 /pmc/articles/PMC10232659/ /pubmed/37244159 http://dx.doi.org/10.1016/j.ebiom.2023.104633 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Ghiringhelli, François
Bibeau, Frederic
Greillier, Laurent
Fumet, Jean-David
Ilie, Alis
Monville, Florence
Laugé, Caroline
Catteau, Aurélie
Boquet, Isabelle
Majdi, Amine
Morgand, Erwan
Oulkhouir, Youssef
Brandone, Nicolas
Adam, Julien
Sbarrato, Thomas
Kassambara, Alboukadel
Fieschi, Jacques
Garcia, Stéphane
Lepage, Anne Laure
Tomasini, Pascale
Galon, Jérôme
Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer
title Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer
title_full Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer
title_fullStr Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer
title_full_unstemmed Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer
title_short Immunoscore immune checkpoint using spatial quantitative analysis of CD8 and PD-L1 markers is predictive of the efficacy of anti- PD1/PD-L1 immunotherapy in non-small cell lung cancer
title_sort immunoscore immune checkpoint using spatial quantitative analysis of cd8 and pd-l1 markers is predictive of the efficacy of anti- pd1/pd-l1 immunotherapy in non-small cell lung cancer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232659/
https://www.ncbi.nlm.nih.gov/pubmed/37244159
http://dx.doi.org/10.1016/j.ebiom.2023.104633
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