| Title: |
Multiplex Analysis of Intratumoural Immune Infiltrate and Prognosis in Patients with Stage II-III Colorectal Cancer from the SCOT and QUASAR 2 Trials : A Retrospective Analysis |
| Authors: |
Frei, Anja L; McGuigan, Anthony; Sinha, Ritik R A K; Jabbar, Faiz; Gneo, Luciana; Tomasevic, Tijana; Harkin, Andrea; Iveson, Tim; Saunders, Mark P; Oien, Karin A; Maka, Noori; Pezzella, Francesco; Campo, Leticia; Browne, Molly; Glaire, Mark; Kildal, Wanja; Danielsen, Havard E; Hay, Jennifer; Edwards, Joanne; Sansom, Owen; Kelly, Caroline; Tomlinson, Ian; Kerr, Rachel; Kerr, David; Domingo, Enric; TransSCOT consortium; Church, David N; Koelzer, Viktor H |
| Source: |
Frei, Anja L; McGuigan, Anthony; Sinha, Ritik R A K; Jabbar, Faiz; Gneo, Luciana; Tomasevic, Tijana; Harkin, Andrea; Iveson, Tim; Saunders, Mark P; Oien, Karin A; Maka, Noori; Pezzella, Francesco; Campo, Leticia; Browne, Molly; Glaire, Mark; Kildal, Wanja; Danielsen, Havard E; Hay, Jennifer; Edwards, Joanne; Sansom, Owen; Kelly, Caroline; Tomlinson, Ian; Kerr, Rachel; Kerr, David; Domingo, Enric; TransSCOT consortium; Church, David N; Koelzer, Viktor H (2024). Multiplex Analysis of Intratumoural Immune Infiltrate and Prognosis in Patients with Stage II-III Colorectal Cancer from the SCOT and QUASAR 2 Trials : A Retrospective Analysis. Lancet Oncology, 25(2):198-211. |
| Publisher Information: |
Elsevier |
| Publication Year: |
2024 |
| Collection: |
University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| Subject Terms: |
Institute of Pathology and Molecular Pathology; 610 Medicine & health |
| Description: |
BACKGROUND Tumour-infiltrating CD8$^{+}$ cytotoxic T cells confer favourable prognosis in colorectal cancer. The added prognostic value of other infiltrating immune cells is unclear and so we sought to investigate their prognostic value in two large clinical trial cohorts. METHODS We used multiplex immunofluorescent staining of tissue microarrays to assess the densities of CD8$^{+}$, CD20$^{+}$, FoxP3$^{+}$, and CD68$^{+}$ cells in the intraepithelial and intrastromal compartments from tumour samples of patients with stage II-III colorectal cancer from the SCOT trial (ISRCTN59757862), which examined 3 months versus 6 months of adjuvant oxaliplatin-based chemotherapy, and from the QUASAR 2 trial (ISRCTN45133151), which compared adjuvant capecitabine with or without bevacizumab. Both trials included patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1. Immune marker predictors were analysed by multiple regression, and the prognostic and predictive values of markers for colorectal cancer recurrence-free interval by Cox regression were assessed using the SCOT cohort for discovery and QUASAR 2 cohort for validation. FINDINGS After exclusion of cases without tissue microarrays and with technical failures, and following quality control, we included 2340 cases from the SCOT trial and 1069 from the QUASAR 2 trial in our analysis. Univariable analysis of associations with recurrence-free interval in cases from the SCOT trial showed a strong prognostic value of intraepithelial CD8 (CD8$^{IE}$) as a continuous variable (hazard ratio [HR] for 75th vs 25th percentile [75vs25] 0·73 [95% CI 0·68-0·79], p=2·5 × 10$^{-16}$), and of intrastromal FoxP3 (FoxP3$^{IS}$; 0·71 [0·64-0·78], p=1·5 × 10$^{-13}$) but not as strongly in the epithelium (FoxP3$^{IE}$; 0·89 [0·84-0·96], p=1·5 × 10$^{-4}$). Associations of other markers with recurrence-free interval were moderate. CD8$^{IE}$ and FoxP3$^{IS}$ retained independent prognostic value in bivariable and multivariable analysis, and, ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1470-2045 |
| Relation: |
https://www.zora.uzh.ch/id/eprint/267297/1/Frei_thelancet_2024.pdf; info:pmid/38301689; urn:issn:1470-2045 |
| Availability: |
https://www.zora.uzh.ch/id/eprint/267297/; https://www.zora.uzh.ch/id/eprint/267297/1/Frei_thelancet_2024.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.22F8F127 |
| Database: |
BASE |