Prognostic value of intra‐tumoral CD8+/FoxP3+ lymphocyte ratio in patients with resected colorectal cancer liver metastasis |
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| Authors: | Kostandinos Sideras MD PhD Boris Galjart Angela Vasaturo PhD Alexander Pedroza‐Gonzalez PhD Katharina Biermann MD PhD Shanta Mancham Alex L Nigg Bettina E Hansen PhD Hans A Stoop PhD Guoying Zhou MD Cornelis Verhoef MD PhD Stefan Sleijfer MD PhD Dave Sprengers MD PhD Jaap Kwekkeboom PhD Marco J Bruno MD PhD |
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| Institution: | 1. Erasmus MC‐University Medical Center, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands;2. Department of Surgical Oncology, Erasmus MC‐University Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands;3. Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands;4. Department of Pathology, Erasmus MC‐University Medical Center, Rotterdam, The Netherlands;5. Department of Medical Oncology, Erasmus MC‐University Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands |
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| Abstract: | Background and Objectives Patients with isolated colorectal‐cancer‐liver‐metastases (CRCLM) frequently undergo metastatectomy. Tumor‐infiltrating‐lymphocytes (TILs) have prognostic potential in the setting of primary colorectal cancer, however, their role in CRCLM is less studied. We aimed to study the spatial distribution and prognostic role of tumor‐infiltrating CD8+ cytotoxic T‐cells and FoxP3+ regulatory T‐cells at the metastatic site of CRCLM patients. Methods TILs were isolated from fresh metastatic tissues of 47 patients with CRCLM. Archived paraffin‐embedded tissue, from the same patients, was retrieved. CD8+ and FoxP3+ cells, both in the intra‐tumoral and the peri‐tumoral compartments, were measured by immunohistochemistry on full tissue sections. Proportions of cytotoxic T‐cells (CD8+) and regulatory T‐cells (CD4+CD25+FoxP3+), within CD45+TILs, were measured by flow‐cytometry. Results By immunohistochemistry, individual densities of intra‐tumoral or peri‐tumoral CD8+ and FoxP3+ cells were not prognostic of survival. However, the intra‐tumoral, but not the peri‐tumoral, CD8+/FoxP3+ ratio was an independent predictor of survival (HR 0.43, 95%CI 0.19‐0.95, P = 0.032). By flow cytometry, the intra‐tumoral CD8+/regulatory T‐cell ratio was also an independent predictor of survival (HR 0.45, 95%CI 0.20‐0.99, P = 0.044). Conclusions The ratio of cytotoxic (CD8+) to regulatory (FoxP3+) T‐cells, in the intra‐tumoral compartment, but not in the peri‐tumoral compartment, can predict survival after resection of CRCLM. |
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| Keywords: | biomarkers colorectal cancer FoxP3 metastasis tumor infiltrating lymphocytes |
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