PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesothelioma
Background Few tissue biomarkers exist to date that could enrich patient with cancer populations to benefit from immune checkpoint blockade by programmed cell death protein 1/ligand-1 (PD-/L-1) inhibitors. PD-L1 expression has value in this context in some tumor types but is an imperfect predictor o...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2023-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/10/e007585.full |
| _version_ | 1797628647122665472 |
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| author | Solange Peters Urania Dafni Panagiota Zygoura Sanjay Popat Mary O'Brien Rolf A Stahel Alessandra Curioni-Fontecedro Georges Coukos Amy Roy Riyaz Shah Krisztian Homicsko James Spicer Stephen P Finn David Gilligan Maxim Norkin Stephanie Tissot Nicholas Shakarishvili Anthony Pope Patricia Fisher Sylvie Rusakiewicz Ekaterina Fortis Nesa Marti Roswitha Kammler |
| author_facet | Solange Peters Urania Dafni Panagiota Zygoura Sanjay Popat Mary O'Brien Rolf A Stahel Alessandra Curioni-Fontecedro Georges Coukos Amy Roy Riyaz Shah Krisztian Homicsko James Spicer Stephen P Finn David Gilligan Maxim Norkin Stephanie Tissot Nicholas Shakarishvili Anthony Pope Patricia Fisher Sylvie Rusakiewicz Ekaterina Fortis Nesa Marti Roswitha Kammler |
| author_sort | Solange Peters |
| collection | DOAJ |
| description | Background Few tissue biomarkers exist to date that could enrich patient with cancer populations to benefit from immune checkpoint blockade by programmed cell death protein 1/ligand-1 (PD-/L-1) inhibitors. PD-L1 expression has value in this context in some tumor types but is an imperfect predictor of clinical benefit. In malignant pleural mesothelioma, PD-L1 expression is not predictive of the benefit from PD-1 blockade. We aimed to identify novel markers in malignant pleural mesothelioma to select patients better.Methods We performed a multiplex-immune histochemistry analysis of tumor samples from the phase III PROMISE-meso study, which randomized 144 pretreated patients to receive either pembrolizumab or standard second-line chemotherapy. Our panel focused on CD8+T cell, CD68+macrophages, and the expression of PD-1 and PD-L1 on these and cancer cells. We analyzed single and double positive cells within cancer tissues (infiltrating immune cells) and in the stroma. In addition, we performed cell neighborhood analysis. The cell counts were compared with clinical outcomes, including responses, progression-free and overall survivals.Results We confirmed the absence of predictive value for PD-L1 in this cohort of patients. Furthermore, total CD8 T cells, CD68+macrophages, or inflammatory subtypes (desert, excluded, inflamed) did not predict outcomes. In contrast, PD-1-expressing CD8+T cells (exhausted T cells) and PD-1-expressing CD68+macrophages were both independent predictors of progression-free survival benefit from pembrolizumab. Patients with tumors simultaneously harboring PD1+T cells and PD-1+macrophages benefited the most from immune therapy.Conclusion We analyzed a large cohort of patients within a phase III study and found that not only PD-1+CD8 T cells but also PD-1+CD68+ macrophages are predictive. This data provides evidence for the first time for the existence of PD-1+macrophages in mesothelioma and their clinical relevance for immune checkpoint blockade. |
| first_indexed | 2024-03-11T10:41:45Z |
| format | Article |
| id | doaj.art-6dd7fca327104b5ea4d8c47266ef755b |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-03-11T10:41:45Z |
| publishDate | 2023-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-6dd7fca327104b5ea4d8c47266ef755b2023-11-14T08:50:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-10-01111010.1136/jitc-2023-007585PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesotheliomaSolange Peters0Urania Dafni1Panagiota Zygoura2Sanjay Popat3Mary O'Brien4Rolf A Stahel5Alessandra Curioni-Fontecedro6Georges Coukos7Amy Roy8Riyaz Shah9Krisztian Homicsko10James Spicer11Stephen P Finn12David Gilligan13Maxim Norkin14Stephanie Tissot15Nicholas Shakarishvili16Anthony Pope17Patricia Fisher18Sylvie Rusakiewicz19Ekaterina Fortis20Nesa Marti21Roswitha Kammler2218 Agora Research Center, Swiss Cancer Center Leman, Lausanne, Switzerland3 ETOP Statistical Center, Frontier Science Foundation - Hellas, Athens, Greece3 ETOP Statistical Center, Frontier Science Foundation - Hellas, Athens, Greece5 Lung Unit, Royal Marsden Hospital NHS Trust, London, UK8 Department of Oncology, Royal Marsden Hospital NHS Trust, London, UK19 President, ETOP IBCSG Partners Foundation, Bern, Switzerland6 Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland1 Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland13 Department of Medical Oncology, University Hospitals Plymouth NHS Trust, Plymouth, UK10 Department of Medical Oncology, Kent Oncology Centre, Maidstone, UK1 Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland12 Comprehensive Cancer Center, King`s College London, London, UK16 Molecular Diagnostics and Histopathology, Trinity College, Dublin, Ireland14 Department of Medical Oncology, Addenbrooke`s Hospital, Cambridge, UK1 Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland4 Immune Landscape Laboratory, Centre Thérapies Expérimentales (CTE), Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland1 Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland9 Department of Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Bebington, UK11 Department of Medical Oncology, Weston Park Hospital, Sheffield, UK4 Immune Landscape Laboratory, Centre Thérapies Expérimentales (CTE), Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland1 Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland15 Translational Research Coordination, ETOP IBCSG Partners Foundation, Bern, Switzerland15 Translational Research Coordination, ETOP IBCSG Partners Foundation, Bern, SwitzerlandBackground Few tissue biomarkers exist to date that could enrich patient with cancer populations to benefit from immune checkpoint blockade by programmed cell death protein 1/ligand-1 (PD-/L-1) inhibitors. PD-L1 expression has value in this context in some tumor types but is an imperfect predictor of clinical benefit. In malignant pleural mesothelioma, PD-L1 expression is not predictive of the benefit from PD-1 blockade. We aimed to identify novel markers in malignant pleural mesothelioma to select patients better.Methods We performed a multiplex-immune histochemistry analysis of tumor samples from the phase III PROMISE-meso study, which randomized 144 pretreated patients to receive either pembrolizumab or standard second-line chemotherapy. Our panel focused on CD8+T cell, CD68+macrophages, and the expression of PD-1 and PD-L1 on these and cancer cells. We analyzed single and double positive cells within cancer tissues (infiltrating immune cells) and in the stroma. In addition, we performed cell neighborhood analysis. The cell counts were compared with clinical outcomes, including responses, progression-free and overall survivals.Results We confirmed the absence of predictive value for PD-L1 in this cohort of patients. Furthermore, total CD8 T cells, CD68+macrophages, or inflammatory subtypes (desert, excluded, inflamed) did not predict outcomes. In contrast, PD-1-expressing CD8+T cells (exhausted T cells) and PD-1-expressing CD68+macrophages were both independent predictors of progression-free survival benefit from pembrolizumab. Patients with tumors simultaneously harboring PD1+T cells and PD-1+macrophages benefited the most from immune therapy.Conclusion We analyzed a large cohort of patients within a phase III study and found that not only PD-1+CD8 T cells but also PD-1+CD68+ macrophages are predictive. This data provides evidence for the first time for the existence of PD-1+macrophages in mesothelioma and their clinical relevance for immune checkpoint blockade.https://jitc.bmj.com/content/11/10/e007585.full |
| spellingShingle | Solange Peters Urania Dafni Panagiota Zygoura Sanjay Popat Mary O'Brien Rolf A Stahel Alessandra Curioni-Fontecedro Georges Coukos Amy Roy Riyaz Shah Krisztian Homicsko James Spicer Stephen P Finn David Gilligan Maxim Norkin Stephanie Tissot Nicholas Shakarishvili Anthony Pope Patricia Fisher Sylvie Rusakiewicz Ekaterina Fortis Nesa Marti Roswitha Kammler PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesothelioma Journal for ImmunoTherapy of Cancer |
| title | PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesothelioma |
| title_full | PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesothelioma |
| title_fullStr | PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesothelioma |
| title_full_unstemmed | PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesothelioma |
| title_short | PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesothelioma |
| title_sort | pd 1 expressing macrophages and cd8 t cells are independent predictors of clinical benefit from pd 1 inhibition in advanced mesothelioma |
| url | https://jitc.bmj.com/content/11/10/e007585.full |
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