Tracking in situ checkpoint inhibitor-bound target T cells in patients with checkpoint-induced colitis Article Swipe
Tarun Gupta
,
Agne Antanaviciute
,
Chloe H. Lee
,
Rosana Ottakandathil Babu
,
Anna Aulicino
,
Zoe Christoforidou
,
Paulina Siejka-Zielińska
,
Caitlin O’Brien‐Ball
,
Hannah Chen
,
David Fawkner-Corbett
,
Ana Sousa Gerós
,
Esther Bridges
,
Colleen McGregor
,
Nicole Cianci
,
Eve Fryer
,
Nasullah Khalid Alham
,
Marta Jagielowicz
,
Ana Mafalda Santos
,
Martin Fellermeyer
,
Simon J. Davis
,
Kaushal Parikh
,
Vincent Cheung
,
Lulia Al‐Hillawi
,
Sarah C. Sasson
,
Stephanie Slevin
,
Oliver Brain
,
Elizabeth Bird‐Lieberman
,
S Fourie
,
Richard Johnston
,
Heman Joshi
,
Debabrata Mujamdar
,
Simon Panter
,
Nishant Patodi
,
Sebastian Shaji
,
Jude Tidbury
,
Ajay Kumar Verma
,
Ricardo A. Fernandes
,
Hashem Koohy
,
Alison Simmons
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.ccell.2024.04.010
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.ccell.2024.04.010
The success of checkpoint inhibitors (CPIs) for cancer has been tempered by immune-related adverse effects including colitis. CPI-induced colitis is hallmarked by expansion of resident mucosal IFNγ cytotoxic CD8+ T cells, but how these arise is unclear. Here, we track CPI-bound T cells in intestinal tissue using multimodal single-cell and subcellular spatial transcriptomics (ST). Target occupancy was increased in inflamed tissue, with drug-bound T cells located in distinct microdomains distinguished by specific intercellular signaling and transcriptional gradients. CPI-bound cells were largely CD4+ T cells, including enrichment in CPI-bound peripheral helper, follicular helper, and regulatory T cells. IFNγ CD8+ T cells emerged from both tissue-resident memory (TRM) and peripheral populations, displayed more restricted target occupancy profiles, and co-localized with damaged epithelial microdomains lacking effective regulatory cues. Our multimodal analysis identifies causal pathways and constitutes a resource to inform novel preventive strategies.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.ccell.2024.04.010
- http://www.cell.com/article/S153561082400134X/pdf
- OA Status
- hybrid
- Cited By
- 15
- References
- 96
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4396873966
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4396873966Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1016/j.ccell.2024.04.010Digital Object Identifier
- Title
-
Tracking in situ checkpoint inhibitor-bound target T cells in patients with checkpoint-induced colitisWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-05-01Full publication date if available
- Authors
-
Tarun Gupta, Agne Antanaviciute, Chloe H. Lee, Rosana Ottakandathil Babu, Anna Aulicino, Zoe Christoforidou, Paulina Siejka-Zielińska, Caitlin O’Brien‐Ball, Hannah Chen, David Fawkner-Corbett, Ana Sousa Gerós, Esther Bridges, Colleen McGregor, Nicole Cianci, Eve Fryer, Nasullah Khalid Alham, Marta Jagielowicz, Ana Mafalda Santos, Martin Fellermeyer, Simon J. Davis, Kaushal Parikh, Vincent Cheung, Lulia Al‐Hillawi, Sarah C. Sasson, Stephanie Slevin, Oliver Brain, Elizabeth Bird‐Lieberman, S Fourie, Richard Johnston, Heman Joshi, Debabrata Mujamdar, Simon Panter, Nishant Patodi, Sebastian Shaji, Jude Tidbury, Ajay Kumar Verma, Ricardo A. Fernandes, Hashem Koohy, Alison SimmonsList of authors in order
- Landing page
-
https://doi.org/10.1016/j.ccell.2024.04.010Publisher landing page
- PDF URL
-
https://www.cell.com/article/S153561082400134X/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://www.cell.com/article/S153561082400134X/pdfDirect OA link when available
- Concepts
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Cytotoxic T cell, Biology, Cell biology, Colitis, Cancer research, CD8, Transcriptome, Immune system, Immunology, In vitro, Biochemistry, Gene, Gene expressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
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15Total citation count in OpenAlex
- Citations by year (recent)
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2025: 11, 2024: 4Per-year citation counts (last 5 years)
- References (count)
-
96Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.analysis | 127 |
| abstract_inverted_index.colitis. | 16 |
| abstract_inverted_index.distinct | 67 |
| abstract_inverted_index.inflamed | 59 |
| abstract_inverted_index.pathways | 130 |
| abstract_inverted_index.resident | 24 |
| abstract_inverted_index.resource | 134 |
| abstract_inverted_index.specific | 71 |
| abstract_inverted_index.tempered | 10 |
| abstract_inverted_index.unclear. | 36 |
| abstract_inverted_index.CPI-bound | 40, 77, 87 |
| abstract_inverted_index.cytotoxic | 27 |
| abstract_inverted_index.displayed | 109 |
| abstract_inverted_index.effective | 122 |
| abstract_inverted_index.expansion | 22 |
| abstract_inverted_index.including | 15, 84 |
| abstract_inverted_index.increased | 57 |
| abstract_inverted_index.occupancy | 55, 113 |
| abstract_inverted_index.profiles, | 114 |
| abstract_inverted_index.signaling | 73 |
| abstract_inverted_index.checkpoint | 3 |
| abstract_inverted_index.drug-bound | 62 |
| abstract_inverted_index.enrichment | 85 |
| abstract_inverted_index.epithelial | 119 |
| abstract_inverted_index.follicular | 90 |
| abstract_inverted_index.gradients. | 76 |
| abstract_inverted_index.hallmarked | 20 |
| abstract_inverted_index.identifies | 128 |
| abstract_inverted_index.inhibitors | 4 |
| abstract_inverted_index.intestinal | 44 |
| abstract_inverted_index.multimodal | 47, 126 |
| abstract_inverted_index.peripheral | 88, 107 |
| abstract_inverted_index.preventive | 138 |
| abstract_inverted_index.regulatory | 93, 123 |
| abstract_inverted_index.restricted | 111 |
| abstract_inverted_index.CPI-induced | 17 |
| abstract_inverted_index.constitutes | 132 |
| abstract_inverted_index.single-cell | 48 |
| abstract_inverted_index.strategies. | 139 |
| abstract_inverted_index.subcellular | 50 |
| abstract_inverted_index.co-localized | 116 |
| abstract_inverted_index.microdomains | 68, 120 |
| abstract_inverted_index.populations, | 108 |
| abstract_inverted_index.distinguished | 69 |
| abstract_inverted_index.intercellular | 72 |
| abstract_inverted_index.immune-related | 12 |
| abstract_inverted_index.CD4<sup>+</sup> | 81 |
| abstract_inverted_index.CD8<sup>+</sup> | 28, 97 |
| abstract_inverted_index.tissue-resident | 103 |
| abstract_inverted_index.transcriptional | 75 |
| abstract_inverted_index.transcriptomics | 52 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 97 |
| corresponding_author_ids | https://openalex.org/A5066267866, https://openalex.org/A5028372846, https://openalex.org/A5087699710 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 39 |
| corresponding_institution_ids | https://openalex.org/I2802742124, https://openalex.org/I40120149, https://openalex.org/I4210110594, https://openalex.org/I90344618 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7200000286102295 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.97045768 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |