Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis
Immune checkpoint inhibitors (ICIs) have provided tremendous clinical benefit in several cancer types. However, systemic activation of the immune system also leads to several immune-related adverse events. Of these, ICI-mediated colitis (IMC) occurs frequently and is the one with the highest absolut...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.768957/full |
| _version_ | 1819121726616764416 |
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| author | Harm Westdorp Harm Westdorp Mark W. D. Sweep Mark W. D. Sweep Mark A. J. Gorris Mark A. J. Gorris Frank Hoentjen Frank Hoentjen Marye J. Boers-Sonderen Rachel S. van der Post Michel M. van den Heuvel Berber Piet Berber Piet Annemarie Boleij Haiko J. Bloemendal I. Jolanda M. de Vries |
| author_facet | Harm Westdorp Harm Westdorp Mark W. D. Sweep Mark W. D. Sweep Mark A. J. Gorris Mark A. J. Gorris Frank Hoentjen Frank Hoentjen Marye J. Boers-Sonderen Rachel S. van der Post Michel M. van den Heuvel Berber Piet Berber Piet Annemarie Boleij Haiko J. Bloemendal I. Jolanda M. de Vries |
| author_sort | Harm Westdorp |
| collection | DOAJ |
| description | Immune checkpoint inhibitors (ICIs) have provided tremendous clinical benefit in several cancer types. However, systemic activation of the immune system also leads to several immune-related adverse events. Of these, ICI-mediated colitis (IMC) occurs frequently and is the one with the highest absolute fatality. To improve current treatment strategies, it is important to understand the cellular mechanisms that induce this form of colitis. In this review, we discuss important pathways that are altered in IMC in mouse models and in human colon biopsy samples. This reveals a complex interplay between several types of immune cells and the gut microbiome. In addition to a mechanistic understanding, patients at risk should be identifiable before ICI therapy. Here we propose to focus on T-cell subsets that interact with bacteria after inducing epithelial damage. Especially, intestinal resident immune cells are of interest. This may lead to a better understanding of IMC and provides opportunities for prevention and management. |
| first_indexed | 2024-12-22T06:41:09Z |
| format | Article |
| id | doaj.art-3d7a2cc22242488098febabeb1c8b7f3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T06:41:09Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3d7a2cc22242488098febabeb1c8b7f32022-12-21T18:35:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.768957768957Mechanisms of Immune Checkpoint Inhibitor-Mediated ColitisHarm Westdorp0Harm Westdorp1Mark W. D. Sweep2Mark W. D. Sweep3Mark A. J. Gorris4Mark A. J. Gorris5Frank Hoentjen6Frank Hoentjen7Marye J. Boers-Sonderen8Rachel S. van der Post9Michel M. van den Heuvel10Berber Piet11Berber Piet12Annemarie Boleij13Haiko J. Bloemendal14I. Jolanda M. de Vries15Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Medical Oncology, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Medical Oncology, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, Netherlands Oncode Institute, Nijmegen, NetherlandsDepartment of Gastroenterology, Radboud University Medical Centre, Nijmegen, NetherlandsDivision of Gastroenterology, University of Alberta, Edmonton, AB, CanadaDepartment of Medical Oncology, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Pulmonary Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Pulmonary Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Medical Oncology, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, NetherlandsImmune checkpoint inhibitors (ICIs) have provided tremendous clinical benefit in several cancer types. However, systemic activation of the immune system also leads to several immune-related adverse events. Of these, ICI-mediated colitis (IMC) occurs frequently and is the one with the highest absolute fatality. To improve current treatment strategies, it is important to understand the cellular mechanisms that induce this form of colitis. In this review, we discuss important pathways that are altered in IMC in mouse models and in human colon biopsy samples. This reveals a complex interplay between several types of immune cells and the gut microbiome. In addition to a mechanistic understanding, patients at risk should be identifiable before ICI therapy. Here we propose to focus on T-cell subsets that interact with bacteria after inducing epithelial damage. Especially, intestinal resident immune cells are of interest. This may lead to a better understanding of IMC and provides opportunities for prevention and management.https://www.frontiersin.org/articles/10.3389/fimmu.2021.768957/fullimmune checkpoint inhibitor (ICI)immune-related adverse eventscolitismechanismstreatment |
| spellingShingle | Harm Westdorp Harm Westdorp Mark W. D. Sweep Mark W. D. Sweep Mark A. J. Gorris Mark A. J. Gorris Frank Hoentjen Frank Hoentjen Marye J. Boers-Sonderen Rachel S. van der Post Michel M. van den Heuvel Berber Piet Berber Piet Annemarie Boleij Haiko J. Bloemendal I. Jolanda M. de Vries Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis Frontiers in Immunology immune checkpoint inhibitor (ICI) immune-related adverse events colitis mechanisms treatment |
| title | Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis |
| title_full | Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis |
| title_fullStr | Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis |
| title_full_unstemmed | Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis |
| title_short | Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis |
| title_sort | mechanisms of immune checkpoint inhibitor mediated colitis |
| topic | immune checkpoint inhibitor (ICI) immune-related adverse events colitis mechanisms treatment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.768957/full |
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