Ling Khoon Lin, Pratap Sarah E, Bates Gaynor J, Singh Baljit, Mortensen Neil J, George Bruce D, Warren Bryan F, Piris Juan, Roncador Giovanna, Fox Stephen B, Banham Alison H, Cerundolo Vincenzo
Tumor Immunology Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
Cancer Immun. 2007 Mar 28;7:7.
Recent results have shown a correlation between survival and frequency of tumour infiltrating T lymphocytes in colorectal cancer patients. However, it remains unclear whether the frequency of regulatory T cells is higher in colorectal cancer as compared to normal colon. To address this question we analysed the frequency and function of regulatory T cells in the peripheral blood and tumour infiltrating lymphocytes of colorectal cancer patients. The proportion of regulatory T cells in the peripheral blood of colorectal cancer patients (mean 8%) was significantly higher than that in normal controls (mean 2.2%). There were significantly more regulatory T cells in tumour infiltrating lymphocytes (mean 19.2%) compared to lymphocytes from an autologous non-malignant portion of the colon (mean 9%). Regulatory T cells from colorectal cancer patients were FOXP3 positive and suppressed the proliferation of autologous CD4+ CD25- cells. A higher density of tumour infiltrating regulatory T cells was found in patients with advanced as compared to early disease. These results support the hypothesis that increased numbers of regulatory T cells in the blood and tumours of colorectal cancer patients may influence the immune response against cancer and suggest that strategies to overcome regulatory T cell activity may be beneficial in the treatment of human colorectal cancer.
近期研究结果显示,在结直肠癌患者中,肿瘤浸润性T淋巴细胞的存活率与频率之间存在相关性。然而,与正常结肠相比,结直肠癌中调节性T细胞的频率是否更高仍不清楚。为了解决这个问题,我们分析了结直肠癌患者外周血和肿瘤浸润淋巴细胞中调节性T细胞的频率和功能。结直肠癌患者外周血中调节性T细胞的比例(平均8%)显著高于正常对照组(平均2.2%)。与来自结肠自体非恶性部分的淋巴细胞(平均9%)相比,肿瘤浸润淋巴细胞中的调节性T细胞明显更多(平均19.2%)。来自结直肠癌患者的调节性T细胞FOXP3呈阳性,并抑制自体CD4+CD25-细胞的增殖。与早期疾病患者相比,晚期患者肿瘤浸润调节性T细胞的密度更高。这些结果支持了这样一种假设,即结直肠癌患者血液和肿瘤中调节性T细胞数量的增加可能会影响针对癌症的免疫反应,并表明克服调节性T细胞活性的策略可能对人类结直肠癌的治疗有益。