Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden.
Br J Cancer. 2014 May 13;110(10):2551-9. doi: 10.1038/bjc.2014.161. Epub 2014 Mar 27.
To find improved tools for prognostic evaluation in patients with colorectal cancer (CRC), we have analysed how infiltration of cytotoxic T lymphocytes (CD8(+)) and regulatory T lymphocytes (FoxP3(+)) correlates to prognosis, not only according to quantity and relation, but also to subsite within tumours of different molecular characteristics (microsatellite instability and CpG island methylator phenotype status).
CD8 and FOXP3 expression was evaluated by immunohistochemistry in 426 archival tumour tissue samples from patients surgically resected for CRC. The average infiltration of CD8(+) and FOXP3(+) cells was assessed along the tumour invasive front, in the tumour centre and within the tumour epithelium (intraepithelial).
We found that infiltration of CD8(+) T lymphocytes within the tumour epithelium provided the strongest prognostic information (P<0.001). At the tumour invasive front and tumour centre, FOXP3 expression withheld the strongest association to prognosis (P<0.001), suggesting FOXP3(+) T-lymphocyte infiltration to be a better prognostic tool than CD8(+) T lymphocytes at these intratumoural subsites. We further analysed the possible prognostic impact of the relation between these T-cell subsets, finding that a high intraepithelial CD8 expression was associated with a better patient outcome, independent of FOXP3 infiltration. In groups of low intraepithelial CD8 expression, however, a high infiltration rate of FOXP3(+) cells at the tumour invasive front, significantly improved prognosis.
Analyses of intraepithelial infiltration of CD8(+) T lymphocytes, infiltration of FOXP3(+) T lymphocytes at the tumour front or centre, and the relation between these subsets, may be a valuable tool for predicting prognosis in colon cancer.
为了寻找改善结直肠癌（CRC）患者预后评估的工具，我们分析了细胞毒性 T 淋巴细胞（CD8(+)）和调节性 T 淋巴细胞（FoxP3(+)）浸润与预后的相关性，不仅根据数量和关系，还根据不同分子特征（微卫星不稳定性和 CpG 岛甲基化表型状态）肿瘤内的亚部位进行分析。
对 426 例接受结直肠癌手术切除的患者的存档肿瘤组织样本进行 CD8 和 FOXP3 表达的免疫组织化学分析。评估 CD8(+)和 FOXP3(+)细胞在肿瘤侵袭前沿、肿瘤中心和肿瘤上皮内（上皮内）的平均浸润情况。
我们发现肿瘤上皮内 CD8(+)T 淋巴细胞浸润提供了最强的预后信息（P<0.001）。在肿瘤侵袭前沿和肿瘤中心，FOXP3 表达与预后的相关性最强（P<0.001），这表明 FOXP3(+)T 淋巴细胞浸润在这些肿瘤内亚部位比 CD8(+)T 淋巴细胞更能作为预后工具。我们进一步分析了这些 T 细胞亚群之间关系的可能预后影响，发现上皮内 CD8 高表达与患者的更好预后相关，独立于 FOXP3 浸润。然而，在低上皮内 CD8 表达的组中，肿瘤侵袭前沿 FOXP3(+)细胞的高浸润率显著改善了预后。
分析 CD8(+)T 淋巴细胞的上皮内浸润、肿瘤前沿或中心的 FOXP3(+)T 淋巴细胞浸润以及这些亚群之间的关系，可能是预测结肠癌预后的有价值的工具。
