Skip to main content

Research Repository

Advanced Search

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.

Activated tissue resident memory T-cells (CD8+CD103+CD39+) uniquely predict survival in left sided “immune-hot” colorectal cancers Thumbnail


Authors

Shahd Talhouni

Wakkas Fadhil

Lara Field

Kelly Hunter

Sogand Makhsous

Alexandre Maciel-Guerra

Nayandeep Kaur

Ausrine Nestarenkaite

Arvydas Laurinavicius

Benjamin E. Willcox



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., Maciel-Guerra, A., Kaur, N., Nestarenkaite, A., Laurinavicius, A., Willcox, B. E., Dottorini, T., Spendlove, I., Jackson, A. M., Ilyas, M., & 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
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

Files





You might also like



Downloadable Citations