Format

Send to

Choose Destination
Br J Cancer. 2019 Aug 7. doi: 10.1038/s41416-019-0540-4. [Epub ahead of print]

Tumour-infiltrating CD8+ lymphocytes and colorectal cancer recurrence by tumour and nodal stage.

Author information

1
Cancer Genomics and Immunology Group, The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
2
Department of Oncology, University of Oxford, Oxford, UK.
3
Department of Molecular Oncology, Institute for Cancer Research & K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway.
4
Department of Gastroenterological Surgery & K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway.
5
Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
6
Department of Statistics, University of Oxford, Oxford, UK.
7
Department of Histopathology, UCL, Rockefeller Building, University Street, London, WC1E 6JJ, UK.
8
Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
9
Department of Informatics, University of Oslo, Oslo, Norway.
10
Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, OX3 9 DU, UK.
11
Oxford Cancer Centre, Churchill Hospital, Oxford University Hospitals Foundation NHS Trust, Oxford, UK.
12
Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
13
Cancer Genomics and Immunology Group, The Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK. dchurch@well.ox.ac.uk.
14
Oxford Cancer Centre, Churchill Hospital, Oxford University Hospitals Foundation NHS Trust, Oxford, UK. dchurch@well.ox.ac.uk.
15
Oxford NIHR Comprehensive Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. dchurch@well.ox.ac.uk.

Abstract

BACKGROUND:

Intratumoural T-cell infiltrate intensity cortes wrelaith clinical outcome in stage II/III colorectal cancer (CRC). We aimed to determine whether this association varies across this heterogeneous group.

METHODS:

We performed a pooled analysis of 1804 CRCs from the QUASAR2 and VICTOR trials. Intratumoural CD8+ and CD3+ densities were quantified by immunohistochemistry in tissue microarray (TMA) cores, and their association with clinical outcome analysed by Cox regression. We validated our results using publicly available gene expression data in a pooled analysis of 1375 CRCs from seven independent series.

RESULTS:

In QUASAR2, intratumoural CD8+ was a stronger predictor of CRC recurrence than CD3+ and showed similar discriminative ability to both markers in combination. Pooled multivariable analysis of both trials showed increasing CD8+ density was associated with reduced recurrence risk independent of confounders including DNA mismatch repair deficiency, POLE mutation and chromosomal instability (multivariable hazard ratio [HR] for each two-fold increase = 0.92, 95%CI = 0.87-0.97, P = 3.6 × 10-3). This association was not uniform across risk strata defined by tumour and nodal stage: absent in low-risk (pT3,N0) cases (HR = 1.03, 95%CI = 0.87-1.21, P = 0.75), modest in intermediate-risk (pT4,N0 or pT1-3,N1-2) cases (HR = 0.92, 95%CI = 0.86-1.0, P = 0.046) and strong in high-risk (pT4,N1-2) cases (HR = 0.87, 95%CI = 0.79-0.97, P = 9.4 × 10-3); PINTERACTION = 0.090. Analysis of tumour CD8A expression in the independent validation cohort revealed similar variation in prognostic value across risk strata (PINTERACTION = 0.048).

CONCLUSIONS:

The prognostic value of intratumoural CD8+ cell infiltration in stage II/III CRC varies across tumour and nodal risk strata.

PMID:
31388185
DOI:
10.1038/s41416-019-0540-4

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for Norwegian BIBSYS system
Loading ...
Support Center