Shahd Talhouni
Activated tissue resident memory T-cells (CD8+CD103+CD39+) uniquely predict survival in left sided “immune-hot” colorectal cancers
Talhouni, Shahd; Fadhil, Wakkas; Mongan, Nigel P.; Field, Lara; Hunter, Kelly; Makhsous, Sogand; Maciel-Guerra, Alexandre; Kaur, Nayandeep; Nestarenkaite, Ausrine; Laurinavicius, Arvydas; Willcox, Benjamin E.; Dottorini, Tania; Spendlove, Ian; Jackson, Andrew M.; Ilyas, Mohammad; Ramage, Judith M.
Authors
Wakkas Fadhil
NIGEL MONGAN nigel.mongan@nottingham.ac.uk
Professor of Oncology
Lara Field
Kelly Hunter
Sogand Makhsous
Alexandre Maciel-Guerra
Nayandeep Kaur
Ausrine Nestarenkaite
Arvydas Laurinavicius
Benjamin E. Willcox
TANIA DOTTORINI TANIA.DOTTORINI@NOTTINGHAM.AC.UK
Professor of Bioinformatics
IAN SPENDLOVE IAN.SPENDLOVE@NOTTINGHAM.AC.UK
Associate Professor
ANDREW JACKSON ANDREW.JACKSON@NOTTINGHAM.AC.UK
Associate Professor
MOHAMMAD ILYAS mohammad.ilyas@nottingham.ac.uk
Professor of Pathology
JUDITH RAMAGE JUDITH.RAMAGE@NOTTINGHAM.AC.UK
Associate Professor
Abstract
Introduction: Characterization of the tumour immune infiltrate (notably CD8+ T-cells) has strong predictive survival value for cancer patients. Quantification of CD8 T-cells alone cannot determine antigenic experience, as not all infiltrating T-cells recognize tumour antigens. Activated tumour-specific tissue resident memory CD8 T-cells (TRM) can be defined by the co-express of CD103, CD39 and CD8. We investigated the hypothesis that the abundance and localization of TRM provides a higher-resolution route to patient stratification. Methods: A comprehensive series of 1000 colorectal cancer (CRC) were arrayed on a tissue microarray, with representative cores from three tumour locations and the adjacent normal mucosa. Using multiplex immunohistochemistry we quantified and determined the localization of TRM. Results: Across all patients, activated TRM were an independent predictor of survival, and superior to CD8 alone. Patients with the best survival had immune-hot tumours heavily infiltrated throughout with activated TRM. Interestingly, differences between right- and left-sided tumours were apparent. In left-sided CRC, only the presence of activated TRM (and not CD8 alone) was prognostically significant. Patients with low numbers of activated TRM cells had a poor prognosis even with high CD8 T-cell infiltration. In contrast, in right-sided CRC, high CD8 T-cell infiltration with low numbers of activated TRM was a good prognosis. Conclusion: The presence of high intra-tumoural CD8 T-cells alone is not a predictor of survival in left-sided CRC and potentially risks under treatment of patients. Measuring both high tumour-associated TRM and total CD8 T-cells in left-sided disease has the potential to minimize current under-treatment of patients. The challenge will be to design immunotherapies, for left-sided CRC patients with high CD8 T-cells and low activate TRM,that result in effective immune responses and thereby improve patient survival.
Citation
Talhouni, S., Fadhil, W., Mongan, N. P., Field, L., Hunter, K., Makhsous, S., …Ramage, J. M. (2023). Activated tissue resident memory T-cells (CD8+CD103+CD39+) uniquely predict survival in left sided “immune-hot” colorectal cancers. Frontiers in Immunology, 14, Article 1057292. https://doi.org/10.3389/fimmu.2023.1057292
Journal Article Type | Article |
---|---|
Acceptance Date | Apr 21, 2023 |
Online Publication Date | May 11, 2023 |
Publication Date | Jan 1, 2023 |
Deposit Date | May 17, 2023 |
Publicly Available Date | May 18, 2023 |
Journal | Frontiers in Immunology |
Electronic ISSN | 1664-3224 |
Publisher | Frontiers Media SA |
Peer Reviewed | Peer Reviewed |
Volume | 14 |
Article Number | 1057292 |
DOI | https://doi.org/10.3389/fimmu.2023.1057292 |
Keywords | cancer, multiplex IHC/IF, T-cells, colorectal cancer, immune microenvironment, tissue resident T cells, CD8 T-cells |
Public URL | https://nottingham-repository.worktribe.com/output/20835062 |
Publisher URL | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1057292/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Immunology&id=1057292 |
Additional Information | School of Medicine University of Nottingham Biodiscovery Institute |
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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