M J M Gooden

Publications (3)15.13 Total impact

• Source

  Available from: Toos Daemen

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

  M J M Gooden, G H de Bock, N Leffers, T Daemen, H W Nijman
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  ABSTRACT: 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. 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. 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. 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.
  British Journal of Cancer 05/2011; 105(1):93-103. · 5.04 Impact Factor
• Source

  Available from: Toos Daemen

  Article: Identification of genes and pathways associated with cytotoxic T lymphocyte infiltration of serous ovarian cancer.

  N Leffers, R S N Fehrmann, M J M Gooden, U R J Schulze, K A Ten Hoor, H Hollema, H M Boezen, T Daemen, S de Jong, H W Nijman, A G J van der Zee
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  ABSTRACT: Tumour-infiltrating lymphocytes (TILs) are predictors of disease-specific survival (DSS) in ovarian cancer. It is largely unknown what factors contribute to lymphocyte recruitment. Our aim was to evaluate genes and pathways contributing to infiltration of cytotoxic T lymphocytes (CTLs) in advanced-stage serous ovarian cancer. For this study global gene expression was compared between low TIL (n=25) and high TIL tumours (n=24). The differences in gene expression were evaluated using parametric T-testing. Selectively enriched biological pathways were identified with gene set enrichment analysis. Prognostic influence was validated in 157 late-stage serous ovarian cancer patients. Using immunohistochemistry, association of selected genes from identified pathways with CTL was validated. The presence of CTL was associated with 320 genes and 23 pathways (P<0.05). In addition, 54 genes and 8 pathways were also associated with DSS in our validation cohort. Immunohistochemical evaluation showed strong correlations between MHC class I and II membrane expression, parts of the antigen processing and presentation pathway, and CTL recruitment. Gene expression profiling and pathway analyses are valuable tools to obtain more understanding of tumour characteristics influencing lymphocyte recruitment in advanced-stage serous ovarian cancer. Identified genes and pathways need to be further investigated for suitability as therapeutic targets.
  British Journal of Cancer 08/2010; 103(5):685-92. · 5.04 Impact Factor
• Article: Identification of genes and pathways associated with cytotoxic T lymphocyte infiltration of serous ovarian cancer

  N Leffers, R S N Fehrmann, M J M Gooden, U R J Schulze, K A ten Hoor, H Hollema, H M Boezen, T Daemen, S de Jong, H W Nijman, A G J van der Zee
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  ABSTRACT: Background: Methods: Results: Conclusion: Patients and methods Results Discussion References Figures and TablesBackground: Tumour-infiltrating lymphocytes (TILs) are predictors of disease-specific survival (DSS) in ovarian cancer. It is largely unknown what factors contribute to lymphocyte recruitment. Our aim was to evaluate genes and pathways contributing to infiltration of cytotoxic T lymphocytes (CTLs) in advanced-stage serous ovarian cancer.
  British Journal of Cancer 07/2010; 103(5):685-692. · 5.04 Impact Factor