Abstract
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.
Highlights
Solid tumours are commonly infiltrated by several immune cells [1,2,3]
Western Blot Analyses of CD4, CD8, and CD56 In order to investigate the expression profile of lymphocyte subpopulations involved in colorectal carcinogenesis and affected by Th inducing POZ-Kruppel Factor (ThPOK), we evaluated a panel of antibodies specific for proteins which identify CD4+, CD8+ and CD56+ lymphocytes
Western blotting data showed that the levels of CD8 protein had a significant upward increase from normal colorectal mucosa (NM) to CRC, with a slightly detectable band in NM; densitometric ratios were 1.6660.20 for MA and 2.1960.15 for CRC. (Figure 1, panel B; band at 32 kD)
Summary
Solid tumours are commonly infiltrated by several immune cells [1,2,3]. Immune cells play conflicting roles with potential capability either in eliminating or promoting malignancy. In contrast to infiltration of cells responsible for chronic inflammation, the presence of high numbers of lymphocytes, especially T cells, has been reported to be an indicator of good prognosis in many types of cancer [4,5,6,7]. Even if the abundance of tumour-infiltrating T-cells has been associated with improved clinical outcome, in some types of cancer, including the colorectal ones, the influence of immune cells on the prognosis is still a matter of debate. Tumour-infiltrating T-cells may be suggestive of the host immune response to the tumour and represent attractive targets for immunotherapy [9]
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