Cancer stem cells (CSCs) can initiate and maintain tumours and may drive metastasis, recurrence and resistance to anti-neoplastic therapies. Recent evidence suggests that CSCs possess immunomodulatory capabilities that may enable them to evade host anti-cancer immunity to promote tumorigenicity. CSC immunological functions include evasion from immune clearance, induction of clonal anergy or deletion, and activation of regulatory immune cells. We recently identified Interleukin-8 as a crucial factor that sustains the stemness features of thyroid cancer (TC) cells through the induction, among the others, of OCT4 and SOX2 transcription factors. We generated OCT4/SOX2 overexpressing TC cells and analysed their stemness and immunomodulatory properties. We confirmed that TC cell lines overexpressing OCT4/SOX2 showed, compared to control cells, an increase in stemness features. Accordingly, OCT4/SOX2 TC cells displayed increased tumour incidence and growth when injected at limiting number in mice compared to parental cells. Negative regulators of the immune system, including Programmed cell Death-Ligands 1 and 2 (PD-L1/PD-L2) and the enzyme Indoleamine 2,3-dioxygenase (IDO) are often “hijacked” by tumours to restrain the ability of the immune system to mount an effective anti-tumor response. Here, we show that OCT4/SOX2 expressing TC cells display increased PD1, PD-L1/2 and IDO expression both at mRNA and protein levels with respect to parental cells. Consistently, TC cells overexpressing OCT4 and SOX2, when co-cultured with lymphoid cells, caused a reduction of lymphocyte vitality compared to control cells. Thus, OCT4 and SOX2 are not only key regulators of stemness features but also of immunomodulatory properties of TC cells.

Stemness and Immunological Features of Thyroid Cancer Cells

2017

Abstract

Cancer stem cells (CSCs) can initiate and maintain tumours and may drive metastasis, recurrence and resistance to anti-neoplastic therapies. Recent evidence suggests that CSCs possess immunomodulatory capabilities that may enable them to evade host anti-cancer immunity to promote tumorigenicity. CSC immunological functions include evasion from immune clearance, induction of clonal anergy or deletion, and activation of regulatory immune cells. We recently identified Interleukin-8 as a crucial factor that sustains the stemness features of thyroid cancer (TC) cells through the induction, among the others, of OCT4 and SOX2 transcription factors. We generated OCT4/SOX2 overexpressing TC cells and analysed their stemness and immunomodulatory properties. We confirmed that TC cell lines overexpressing OCT4/SOX2 showed, compared to control cells, an increase in stemness features. Accordingly, OCT4/SOX2 TC cells displayed increased tumour incidence and growth when injected at limiting number in mice compared to parental cells. Negative regulators of the immune system, including Programmed cell Death-Ligands 1 and 2 (PD-L1/PD-L2) and the enzyme Indoleamine 2,3-dioxygenase (IDO) are often “hijacked” by tumours to restrain the ability of the immune system to mount an effective anti-tumor response. Here, we show that OCT4/SOX2 expressing TC cells display increased PD1, PD-L1/2 and IDO expression both at mRNA and protein levels with respect to parental cells. Consistently, TC cells overexpressing OCT4 and SOX2, when co-cultured with lymphoid cells, caused a reduction of lymphocyte vitality compared to control cells. Thus, OCT4 and SOX2 are not only key regulators of stemness features but also of immunomodulatory properties of TC cells.
11-dic-2017
Italiano
Università degli Studi di Napoli Federico II
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/145139
Il codice NBN di questa tesi è URN:NBN:IT:UNINA-145139