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

Shahd Talhouni, Wakkas Fadhil, Nigel P. Mongan, Lara Field, Kelly Hunter, Sogand Makhsous, Alexandre Maciel-Guerra, Nayandeep Kaur, Ausrine Nestarenkaite, Arvydas Laurinavicius, Benjamin E. Willcox, Tania Dottorini, Ian Spendlove, Andrew M. Jackson, Mohammad Ilyas, Judith M. Ramage

Research output: Journal PublicationArticlepeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Article number1057292
JournalFrontiers in Immunology
Volume14
DOIs
Publication statusPublished - 2023
Externally publishedYes

Keywords

  • CD8 T-cells
  • T-cells
  • cancer
  • colorectal cancer
  • immune microenvironment
  • multiplex IHC/IF
  • tissue resident T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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