Ward-Hartstonge Kirsten A, McCall John L, McCulloch Timothy R, Kamps Ann-Kristin, Girardin Adam, Cretney Erika, Munro Fran M, Kemp Roslyn A
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
Department of Surgical Sciences, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
Cancer Immunol Immunother. 2017 Apr;66(4):515-522. doi: 10.1007/s00262-016-1951-1. Epub 2017 Jan 23.
Analysis of tumour-infiltrating T cells in colorectal cancer can predict disease-free survival. The Immunoscore, obtained by quantifying tumour-infiltrating CD3 and CD8 T cells, may improve current staging. Effector regulatory T cells are a potently suppressive subset in mice and, while present in human colorectal cancer, their role in patient outcome is unknown. Immunofluorescence was used to analyse immune cell infiltrates in patients with early (stage II) colorectal cancer with (n = 13) and without (n = 19) recurrent disease. CD3 and CD8 were used for the Immunoscore; FOXP3, BLIMP-1 and CD3 to identify effector regulatory T cells. Patients with high Immunoscores had increased disease-free survival compared to patients with low Immunoscores (Log-rank test p < 0.01). Prediction of outcome was further improved by stratifying patients with a low Immunoscore according to CD3FOXP3BLIMP-1 cell infiltration at the invasive margin. Patients with a low Immunoscore and high infiltrate of CD3FOXP3BLIMP-1 cells tended to have better disease-free survival than patients with low Immunoscore and low infiltrate of CD3FOXP3BLIMP-1 cells. Patients with a high Immunoscore had better disease-free survival than patients with a low Immunoscore and low infiltrate of CD3+ FOXP3+ BLIMP-1+ cells (Log-rank test p < 0.001). These results indicate that tumour infiltration with effector regulatory T cells improves the prognostic value of the Immunoscore and implies that these cells may play a role in colorectal cancer patient outcome.
结直肠癌中肿瘤浸润性T细胞的分析可预测无病生存期。通过量化肿瘤浸润性CD3和CD8 T细胞获得的免疫评分可能会改善当前的分期。效应调节性T细胞在小鼠中是一种具有强大抑制作用的亚群,虽然在人类结直肠癌中存在,但其在患者预后中的作用尚不清楚。采用免疫荧光法分析早期(II期)有(n = 13)和无(n = 19)复发性疾病的结直肠癌患者的免疫细胞浸润情况。使用CD3和CD8进行免疫评分;使用FOXP3、BLIMP-1和CD3来识别效应调节性T细胞。与低免疫评分的患者相比,高免疫评分的患者无病生存期延长(对数秩检验p < 0.01)。根据浸润边缘处CD3FOXP3BLIMP-1细胞浸润情况对低免疫评分患者进行分层,可进一步改善预后预测。免疫评分低且CD3FOXP3BLIMP-1细胞浸润高的患者比免疫评分低且CD3FOXP3BLIMP-1细胞浸润低的患者无病生存期往往更好。高免疫评分的患者比免疫评分低且CD3 + FOXP3 + BLIMP-1 + 细胞浸润低的患者无病生存期更好(对数秩检验p < 0.001)。这些结果表明,效应调节性T细胞的肿瘤浸润提高了免疫评分的预后价值,并暗示这些细胞可能在结直肠癌患者的预后中发挥作用。