Department of Cancer Therapy and Research, Kyushu University, Maidashi, Higashi-Ku, Fukuoka, Japan.
Cancer Immunol Immunother. 2010 May;59(5):653-61. doi: 10.1007/s00262-009-0781-9. Epub 2009 Nov 12.
The human immune system consists of a balance between immune surveillance against non-self antigens and tolerance of self-antigens. CD8(+) T cells and CD4(+) regulatory T cells (Tregs) are the main players for immune surveillance and tolerance, respectively. We examined immunohistochemically the immunological balance at the tumor site using 94 surgically resected colorectal cancer tissues. Forkhead box P3 (FOXP3)(+) cells were considered to be Tregs in the present study. The number of intratumoral FOXP3(+) cells (itFOXP3(+) cells) was positively correlated with lymph node metastases (P = 0.030). itCD8(+) T/itFOXP3(+) cell ratio negatively correlated with pathological stages (P = 0.048). Next, relationship between the number of itCD8(+) T cells or itFOXP3(+) cells and survival prognosis in 94 patients who underwent a curative resection was analyzed. Only itCD8(+) T/itFOXP3(+) cell ratio positively correlated with disease-free survival (0.023) and overall survival (P = 0.010). Multivariate analysis indicated that itCD8(+) T/itFOXP3(+) cell ratio is an independent prognostic factor (P = 0.035) of overall survival. The number of itFOXP3(+) cells positively correlated with transforming growth factor-beta TGF-beta production at the tumor site (P = 0.020). In conclusion, itCD8(+) T/itFOXP3(+) cell ratio is a predictive marker for both disease-free survival time and overall survival time in patients with colorectal cancer. Importantly, itCD8(+) T/itFOXP3(+) cell ratio may be an independent prognostic factor. And, tumor-producing TGF-beta may contribute to the increased number of itFOXP3(+) cells.
人体免疫系统由针对非自身抗原的免疫监视和自身抗原耐受之间的平衡组成。CD8(+)T 细胞和 CD4(+)调节性 T 细胞（Tregs）分别是免疫监视和耐受的主要参与者。我们使用 94 例手术切除的结直肠癌组织，通过免疫组织化学方法检查了肿瘤部位的免疫平衡。在本研究中，FOXP3(+)细胞被认为是 Tregs。肿瘤内 FOXP3(+)细胞（itFOXP3(+)细胞）的数量与淋巴结转移呈正相关（P = 0.030）。itCD8(+)T/itFOXP3(+)细胞比值与病理分期呈负相关（P = 0.048）。接下来，分析了 94 例接受根治性切除术的患者中 itCD8(+)T 细胞或 itFOXP3(+)细胞数量与生存预后的关系。只有 itCD8(+)T/itFOXP3(+)细胞比值与无病生存率（0.023）和总生存率（P = 0.010）呈正相关。多变量分析表明，itCD8(+)T/itFOXP3(+)细胞比值是总生存率的独立预后因素（P = 0.035）。肿瘤内 itFOXP3(+)细胞的数量与肿瘤部位转化生长因子-β（TGF-β）的产生呈正相关（P = 0.020）。总之，itCD8(+)T/itFOXP3(+)细胞比值是结直肠癌患者无病生存时间和总生存时间的预测标志物。重要的是，itCD8(+)T/itFOXP3(+)细胞比值可能是独立的预后因素。并且，肿瘤产生的 TGF-β可能导致 itFOXP3(+)细胞数量增加。
