Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity
Background Immunotherapy has revolutionized clinical outcomes for patients suffering from lung cancer, yet relatively few patients sustain long-term durable responses. Recent studies have demonstrated that the tumor immune microenvironment fosters tumorous heterogeneity and mediates both disease pro...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-02-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/2/e005545.full |
| _version_ | 1828044198013566976 |
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| author | Philippe Joubert Azadeh Arabzadeh Valérie Breton Mark Sorin Elham Karimi Morteza Rezanejad Miranda W Yu Lysanne Desharnais Sheri A C McDowell Samuel Doré Benoit Fiset Yuhong Wei Roni Rayes Michele Orain Francois Coulombe Venkata S K Manem Andreanne Gagne Daniela F Quail Jonathan D Spicer Logan A Walsh |
| author_facet | Philippe Joubert Azadeh Arabzadeh Valérie Breton Mark Sorin Elham Karimi Morteza Rezanejad Miranda W Yu Lysanne Desharnais Sheri A C McDowell Samuel Doré Benoit Fiset Yuhong Wei Roni Rayes Michele Orain Francois Coulombe Venkata S K Manem Andreanne Gagne Daniela F Quail Jonathan D Spicer Logan A Walsh |
| author_sort | Philippe Joubert |
| collection | DOAJ |
| description | Background Immunotherapy has revolutionized clinical outcomes for patients suffering from lung cancer, yet relatively few patients sustain long-term durable responses. Recent studies have demonstrated that the tumor immune microenvironment fosters tumorous heterogeneity and mediates both disease progression and response to immune checkpoint inhibitors (ICI). As such, there is an unmet need to elucidate the spatially defined single-cell landscape of the lung cancer microenvironment to understand the mechanisms of disease progression and identify biomarkers of response to ICI.Methods Here, in this study, we applied imaging mass cytometry to characterize the tumor and immunological landscape of immunotherapy response in non-small cell lung cancer by describing activated cell states, cellular interactions and neighborhoods associated with improved efficacy. We functionally validated our findings using preclinical mouse models of cancer treated with anti-programmed cell death protein-1 (PD-1) immune checkpoint blockade.Results We resolved 114,524 single cells in 27 patients treated with ICI, enabling spatial resolution of immune lineages and activation states with distinct clinical outcomes. We demonstrated that CXCL13 expression is associated with ICI efficacy in patients, and that recombinant CXCL13 potentiates anti-PD-1 response in vivo in association with increased antigen experienced T cell subsets and reduced CCR2+ monocytes.Discussion Our results provide a high-resolution molecular resource and illustrate the importance of major immune lineages as well as their functional substates in understanding the role of the tumor immune microenvironment in response to ICIs. |
| first_indexed | 2024-04-10T17:53:16Z |
| format | Article |
| id | doaj.art-b3889797f7b44bc4821c45531186df0a |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-04-10T17:53:16Z |
| publishDate | 2023-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-b3889797f7b44bc4821c45531186df0a2023-02-02T20:00:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-02-0111210.1136/jitc-2022-005545Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunityPhilippe Joubert0Azadeh Arabzadeh1Valérie Breton2Mark Sorin3Elham Karimi4Morteza Rezanejad5Miranda W Yu6Lysanne Desharnais7Sheri A C McDowell8Samuel Doré9Benoit Fiset10Yuhong Wei11Roni Rayes12Michele Orain13Francois Coulombe14Venkata S K Manem15Andreanne Gagne16Daniela F Quail17Jonathan D Spicer18Logan A Walsh19Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaDepartment of Psychology and Computer Science, University of Toronto, Toronto, Ontario, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, Quebec, CanadaInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, Quebec, CanadaInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, Quebec, CanadaInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaRosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, CanadaBackground Immunotherapy has revolutionized clinical outcomes for patients suffering from lung cancer, yet relatively few patients sustain long-term durable responses. Recent studies have demonstrated that the tumor immune microenvironment fosters tumorous heterogeneity and mediates both disease progression and response to immune checkpoint inhibitors (ICI). As such, there is an unmet need to elucidate the spatially defined single-cell landscape of the lung cancer microenvironment to understand the mechanisms of disease progression and identify biomarkers of response to ICI.Methods Here, in this study, we applied imaging mass cytometry to characterize the tumor and immunological landscape of immunotherapy response in non-small cell lung cancer by describing activated cell states, cellular interactions and neighborhoods associated with improved efficacy. We functionally validated our findings using preclinical mouse models of cancer treated with anti-programmed cell death protein-1 (PD-1) immune checkpoint blockade.Results We resolved 114,524 single cells in 27 patients treated with ICI, enabling spatial resolution of immune lineages and activation states with distinct clinical outcomes. We demonstrated that CXCL13 expression is associated with ICI efficacy in patients, and that recombinant CXCL13 potentiates anti-PD-1 response in vivo in association with increased antigen experienced T cell subsets and reduced CCR2+ monocytes.Discussion Our results provide a high-resolution molecular resource and illustrate the importance of major immune lineages as well as their functional substates in understanding the role of the tumor immune microenvironment in response to ICIs.https://jitc.bmj.com/content/11/2/e005545.full |
| spellingShingle | Philippe Joubert Azadeh Arabzadeh Valérie Breton Mark Sorin Elham Karimi Morteza Rezanejad Miranda W Yu Lysanne Desharnais Sheri A C McDowell Samuel Doré Benoit Fiset Yuhong Wei Roni Rayes Michele Orain Francois Coulombe Venkata S K Manem Andreanne Gagne Daniela F Quail Jonathan D Spicer Logan A Walsh Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity Journal for ImmunoTherapy of Cancer |
| title | Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity |
| title_full | Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity |
| title_fullStr | Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity |
| title_full_unstemmed | Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity |
| title_short | Single-cell spatial landscape of immunotherapy response reveals mechanisms of CXCL13 enhanced antitumor immunity |
| title_sort | single cell spatial landscape of immunotherapy response reveals mechanisms of cxcl13 enhanced antitumor immunity |
| url | https://jitc.bmj.com/content/11/2/e005545.full |
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