The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis

• Published in: British journal of cancer Vol. 105; no. 1; pp. 93 - 103
• Main Authors: Gooden, M J M, de Bock, G H, Leffers, N, Daemen, T, Nijman, H W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28-06-2011; Nature Publishing Group
• Subjects: 631/67/580; 692/53/2422; Antigens; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Drug Resistance; Epidemiology; Humans; Immune system; Immunology; Lymphocytes; Lymphocytes, Tumor-Infiltrating - pathology; Medical prognosis; Medical research; Medical sciences; Meta-analysis; Molecular Diagnostics; Molecular Medicine; Neoplasms - diagnosis; Neoplasms - immunology; Oncology; Prognosis; Ratios; Survival analysis; Systematic review; Tumors; Netherlands; meta-analysis; tumour-infiltrating lymphocytes; prognosis; Cancerology; Prognosis; Tumor infiltrating lymphocyte; Malignant tumor; Bibliographic review; Cancer; Metaanalysis
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.189

Background:
Tumour-infiltrating lymphocytes (TILs) are often found in tumours, presumably reflecting an immune response against the tumour. We carried out a systematic review and meta-analysis, aiming to establish pooled estimates for survival outcomes based on the presence of TILs in cancer.
Methods:
A Pubmed and Embase literature search was designed. Studies were included, in which the prognostic significance of intratumoural CD3+, CD4+, CD8+, and FoxP3+ lymphocytes, as well as ratios between these subsets, were determined in solid tumours.
Results:
In pooled analysis, CD3+ TILs had a positive effect on survival with a hazard ratio (HR) of 0.58 (95% confidence interval (CI) 0.43–0.78) for death, as did CD8+ TILs with a HR of 0.71 (95% CI 0.62–0.82). FoxP3+ regulatory TILs were not linked to overall survival, with a HR of 1.19 (95% CI 0.84–1.67). The CD8/FoxP3 ratio produced a more impressive HR (risk of death: HR 0.48, 95% CI 0.34–0.68), but was used in relatively few studies. Sample size and follow-up time seemed to influence study outcomes.
Conclusion:
Any future studies should be carefully designed, to prevent overestimating the effect of TILs on prognosis. In this context, ratios between TIL subsets may be more informative.