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 cancerResearch in context
Summary: 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-Immun...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423001986 |
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| author | François Ghiringhelli Frederic Bibeau Laurent Greillier Jean-David Fumet Alis Ilie Florence Monville Caroline Laugé Aurélie Catteau Isabelle Boquet Amine Majdi Erwan Morgand Youssef Oulkhouir Nicolas Brandone Julien Adam Thomas Sbarrato Alboukadel Kassambara Jacques Fieschi Stéphane Garcia Anne Laure Lepage Pascale Tomasini Jérôme Galon |
| author_facet | François Ghiringhelli Frederic Bibeau Laurent Greillier Jean-David Fumet Alis Ilie Florence Monville Caroline Laugé Aurélie Catteau Isabelle Boquet Amine Majdi Erwan Morgand Youssef Oulkhouir Nicolas Brandone Julien Adam Thomas Sbarrato Alboukadel Kassambara Jacques Fieschi Stéphane Garcia Anne Laure Lepage Pascale Tomasini Jérôme Galon |
| author_sort | François Ghiringhelli |
| collection | DOAJ |
| description | Summary: 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: Veracyte, INSERM, Labex Immuno-Oncology, Transcan ERAnet European project, ARC, SIRIC, CARPEM, Ligue Contre le Cancer, ANR, QNRF, INCa France, Louis Jeantet Prize Foundation. |
| first_indexed | 2024-03-13T09:29:27Z |
| format | Article |
| id | doaj.art-af4bad0461854aff8dc0c5518a34fcbc |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-13T09:29:27Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-af4bad0461854aff8dc0c5518a34fcbc2023-05-26T04:21:42ZengElsevierEBioMedicine2352-39642023-06-0192104633Immunoscore 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 cancerResearch in contextFrançois Ghiringhelli0Frederic Bibeau1Laurent Greillier2Jean-David Fumet3Alis Ilie4Florence Monville5Caroline Laugé6Aurélie Catteau7Isabelle Boquet8Amine Majdi9Erwan Morgand10Youssef Oulkhouir11Nicolas Brandone12Julien Adam13Thomas Sbarrato14Alboukadel Kassambara15Jacques Fieschi16Stéphane Garcia17Anne Laure Lepage18Pascale Tomasini19Jérôme Galon20Platform of Transfer in Biological Oncology, Georges François Leclerc Cancer Center - UNICANCER, Dijon, France; Genomic and Immunotherapy Medical Institute, Dijon University Hospital, Dijon, France; University of Burgundy-Franche Comté, Maison de l'Université Esplanade Erasme, Dijon, France; UMR INSERM 1231, Dijon, France; Department of Medical Oncology, Georges François Leclerc Cancer Center - UNICANCER, Dijon, FranceDepartment of Pathology, Besançon University Hospital, Franche-Comté University, Besançon, France; Department of Pathology, Caen University Hospital, Normandy University, Caen, FranceMultidisciplinary Oncology and Therapeutic Innovations Department, APHM, INSERM, CNRS, CRCM, Hôpital Nord, Aix Marseille University, Marseille, FrancePlatform of Transfer in Biological Oncology, Georges François Leclerc Cancer Center - UNICANCER, Dijon, France; Genomic and Immunotherapy Medical Institute, Dijon University Hospital, Dijon, France; University of Burgundy-Franche Comté, Maison de l'Université Esplanade Erasme, Dijon, France; UMR INSERM 1231, Dijon, France; Department of Medical Oncology, Georges François Leclerc Cancer Center - UNICANCER, Dijon, FrancePlatform of Transfer in Biological Oncology, Georges François Leclerc Cancer Center - UNICANCER, Dijon, FranceVeracyte, Marseille, FranceVeracyte, Marseille, FranceVeracyte, Marseille, FranceVeracyte, Marseille, FranceINSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Equipe Labellisée Ligue Contre le Cancer, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, FranceINSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Equipe Labellisée Ligue Contre le Cancer, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, FranceDepartment of Thoracic Oncology, Caen University Hospital, Normandy University, Caen, FranceEurofins Pathologie, Bd Charles Moretti, Marseille 13014, FranceAnatomie et Cytologie Pathologiques, Hôpital Paris Saint-Joseph, INSERM, Gustave Roussy, Université Paris Saclay, Paris, FranceVeracyte, Marseille, FranceVeracyte, Marseille, FranceVeracyte, Marseille, FranceMultidisciplinary Oncology and Therapeutic Innovations Department, APHM, INSERM, CNRS, CRCM, Hôpital Nord, Aix Marseille University, Marseille, FrancePlatform of Transfer in Biological Oncology, Georges François Leclerc Cancer Center - UNICANCER, Dijon, France; Department of Pathology, Besançon University Hospital, Franche-Comté University, Besançon, FranceMultidisciplinary Oncology and Therapeutic Innovations Department, APHM, INSERM, CNRS, CRCM, Hôpital Nord, Aix Marseille University, Marseille, FranceVeracyte, Marseille, France; INSERM, Laboratory of Integrative Cancer Immunology, Paris, France; Equipe Labellisée Ligue Contre le Cancer, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France; Corresponding author. INSERM, Laboratory of Integrative Cancer Immunology, Cordeliers Research Centre, 15 Rue de l'École de Médecine, Paris 75006, France.Summary: 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: Veracyte, INSERM, Labex Immuno-Oncology, Transcan ERAnet European project, ARC, SIRIC, CARPEM, Ligue Contre le Cancer, ANR, QNRF, INCa France, Louis Jeantet Prize Foundation.http://www.sciencedirect.com/science/article/pii/S2352396423001986Digital pathologyImmunoscore-ICPrognostic markerNon-small cell lung cancerImmunotherapy |
| spellingShingle | François Ghiringhelli Frederic Bibeau Laurent Greillier Jean-David Fumet Alis Ilie Florence Monville Caroline Laugé Aurélie Catteau Isabelle Boquet Amine Majdi Erwan Morgand Youssef Oulkhouir Nicolas Brandone Julien Adam Thomas Sbarrato Alboukadel Kassambara Jacques Fieschi Stéphane Garcia Anne Laure Lepage Pascale Tomasini Jérôme Galon 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 cancerResearch in context EBioMedicine Digital pathology Immunoscore-IC Prognostic marker Non-small cell lung cancer Immunotherapy |
| 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 cancerResearch in context |
| 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 cancerResearch in context |
| 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 cancerResearch in context |
| 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 cancerResearch in context |
| 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 cancerResearch in context |
| 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 cancerresearch in context |
| topic | Digital pathology Immunoscore-IC Prognostic marker Non-small cell lung cancer Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423001986 |
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