Journal article
Tumour-infiltrating CD8+ lymphocytes and colorectal cancer recurrence by tumour and nodal stage
- Abstract:
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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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 752.0KB, Terms of use)
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- Publisher copy:
- 10.1038/s41416-019-0540-4
Authors
- Funding agency for:
- Church, D
- Grant:
- Clinician Scientist Fellowship
- Grant:
- 090532/Z/09/Z
- Clinical Training Fellowship
- Funding agency for:
- Glaire, MA
- Publisher:
- Springer Nature
- Journal:
- British Journal of Cancer More from this journal
- Volume:
- 121
- Pages:
- 474-482
- Publication date:
- 2019-08-07
- Acceptance date:
- 2019-07-18
- DOI:
- EISSN:
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1532-1827
- ISSN:
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0007-0920
- Keywords:
- Pubs id:
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pubs:1030348
- UUID:
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uuid:1a7063af-69fa-4d8b-a174-a4fc1d25f860
- Local pid:
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pubs:1030348
- Source identifiers:
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1030348
- Deposit date:
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2019-07-09
Terms of use
- Copyright holder:
- Glaire et al
- Copyright date:
- 2019
- Notes:
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© The Author(s) 2019
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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