| Title |
Activated tissue resident memory T-cells (CD8+CD103+CD39+) uniquely predict survival in left sided “immune-hot” colorectal cancers / |
| Authors |
Talhouni, Shahd ; Fadhil, Wakkas ; Mongan, Nigel P ; Field, Lara ; Hunter, Kelly ; Makhsous, Sogand ; Maciel-Guerra, Alexandre ; Kaur, Nayandeep ; Nestarenkaitė, Aušrinė ; Laurinavičius, Arvydas ; Willcox, Benjamin E ; Dottorini, Tania ; Spendlove, Ian ; Jackson, Andrew M ; Ilyas, Mohammad ; Ramage, Judith M |
| DOI |
10.3389/fimmu.2023.1057292 |
| Full Text |
|
| Is Part of |
Frontiers in immunology.. Lausanne : Frontiers Media S.A.. 2023, vol. 14, art. no. 1057292, p. [1-15].. eISSN 1664-3224 |
| Keywords [eng] |
cancer ; CD8 T-cells ; colorectal cancer ; immune microenvironment ; multiplex IHC/IF ; T-cells ; tissue resident T cells |
| Abstract [eng] |
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. |
| Published |
Lausanne : Frontiers Media S.A |
| Type |
Journal article |
| Language |
English |
| Publication date |
2023 |
| CC license |
|
