Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy.
PLoS One. 2013;8(1):e54488. doi: 10.1371/journal.pone.0054488. Epub 2013 Jan 17.
We purposed to evaluate the role of Th inducing POZ-Kruppel Factor (ThPOK), a transcriptional regulator of T cell fate, in tumour-induced immune system plasticity in colorectal carcinogenesis. The amounts of CD4+, CD8+ and CD56+ and ThPOK+ cells infiltrate in normal colorectal mucosa (NM), in dysplastic aberrant crypt foci (microadenomas, MA), the earliest detectable lesions in colorectal carcinogenesis, and in colorectal carcinomas (CRC), were measured, and the colocalization of ThPOK with the above-mentioned markers of immune cells was evaluated using confocal microscopy. Interestingly, ThPOK showed a prominent increase since MA. A strong colocalization of ThPOK with CD4 both in NM and in MA was observed, weaker in carcinomas. Surprisingly, there was a peak in the colocalization levels of ThPOK with CD8 in MA, which was evident, although to a lesser extent, in carcinomas, too. In conclusion, according to the data of the present study, ThPOK may be considered a central regulator of the earliest events in the immune system during colorectal cancer development, decreasing the immune response against cancer cells.
我们旨在评估 Th 诱导的 POZ-Kruppel 因子(ThPOK)在结直肠癌发生中的肿瘤诱导免疫系统可塑性中的作用,ThPOK 是 T 细胞命运的转录调节剂。测量了正常结直肠黏膜(NM)、发育异常的异常隐窝灶(微腺瘤,MA)、结直肠癌发生中最早可检测到的病变以及结直肠癌(CRC)中浸润的 CD4+、CD8+和 CD56+和 ThPOK+细胞的数量,并使用共聚焦显微镜评估了 ThPOK 与上述免疫细胞标志物的共定位。有趣的是,自 MA 以来,ThPOK 明显增加。在 NM 和 MA 中均观察到 ThPOK 与 CD4 的强烈共定位,在癌中较弱。令人惊讶的是,在 MA 中 ThPOK 与 CD8 的共定位水平达到峰值,尽管在癌中程度较小,但也很明显。总之,根据本研究的数据,ThPOK 可被认为是结直肠癌发展过程中免疫系统早期事件的中央调节剂,降低了对癌细胞的免疫反应。