Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients.
By H. R. Ali, E. Provenzano, S. Dawson, F. Blows, Bin Liu, M. Shah, H. Earl, C. Poole, L. Hiller, J. Dunn and 11 more. Annals of Oncology, 2014
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BACKGROUND T-cell infiltration in estrogen receptor (ER)-negative breast tumours has been associated with longer survival. To investigate this association and the potential of tumour T-cell infiltration as a prognostic and predictive marker, we have conducted the largest study of T cells in breast cancer to date. PATIENTS AND METHODS Four studies totalling 12 439 patients were used for this work. Cytotoxic (CD8+) and regulatory (forkhead box protein 3, FOXP3+) T cells were quantified using immunohistochemistry (IHC). IHC for CD8 was conducted using available material from all four studies (8978 samples) and for FOXP3 from three studies (5239 samples)-multiple imputation was used to resolve missing data from the remaining patients. Cox regression was used to test for associations with breast cancer-specific survival. RESULTS In ER-negative tumours [triple-negative breast cancer and human epidermal growth factor receptor 2 (human epidermal growth factor receptor 2 (HER2) positive)], presence of CD8+ T cells within the tumour was associated with a 28% [95% confidence interval (CI) 16% to 38%] reduction in the hazard of breast cancer-specific mortality, and CD8+ T cells within the stroma with a 21% (95% CI 7% to 33%) reduction in hazard. In ER-positive HER2-positive tumours, CD8+ T cells within the tumour were associated with a 27% (95% CI 4% to 44%) reduction in hazard. In ER-negative disease, there was evidence for greater benefit from anthracyclines in the National Epirubicin Adjuvant Trial in patients with CD8+ tumours [hazard ratio (HR) = 0.54; 95% CI 0.37-0.79] versus CD8-negative tumours (HR = 0.87; 95% CI 0.55-1.38). The difference in effect between these subgroups was significant when limited to cases with complete data (P heterogeneity = 0.04) and approached significance in imputed data (P heterogeneity = 0.1). CONCLUSIONS The presence of CD8+ T cells in breast cancer is associated with a significant reduction in the relative risk of death from disease in both the ER-negative [supplementary Figure S1, available at Annals of Oncology online] and the ER-positive HER2-positive subtypes. Tumour lymphocytic infiltration may improve risk stratification in breast cancer patients classified into these subtypes. NEAT ClinicalTrials.gov: NCT00003577.
Subfields: Cancer Research, Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/2a4bc136af115a8ff67a3baef47b0d6a91b9d9c7
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Citations in the corpus
- The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. (2015, result): “However, recently published studies [11, 31, 33] using TMAs and well-annotated clinical datasets show that results are concordant with other studies in the field using mostly biomarker-based determinations of TILs subsets, not H&E determinations of general TILs.”
- Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer. (2018, positive): “…consistent with the correlations observed between CD8+ or FOXP3+ T lymphocytes with CD3+ T cells (Figure S3F) and suggest that better survival of TNBC patients is associated with a global high T cell infiltration, as previously reported (DeNardo et al., 2011; Liu et al., 2012; Ali et al., 2014).”