Abstract
BackgroundAt the beginning of tumorigenesis, newly born cancer cells must successfully avoid attack by the immune system. Although most abnormal cells are efficiently identified and destroyed by the immune system, particularly by NK cells, the molecular mechanisms by which newly born cancer cells evade NK cell surveillance are not fully understood.MethodsNK cell resistance of highly tumorigenic population of human prostate cancer (PCa) cells were confirmed by xenograft in SCID mice with or without NK cell neutralization. The mechanisms by which the tumorigenic PCa cells evaded NK cell attack were investigated by RNAseq, ChIPseq, generation of several transformants and xenograft in SCID mice.ResultsHere, we show that PCa cells have a strengthened ability to escape NK cell attack due to NANOG, a pluripotent-related transcription factor, mediating the repression of ICAM1, a cell adhesion molecule, during tumorigenesis. Mechanistically, NANOG directly binds to the region upstream of ICAM1. As the binding between NANOG and the upstream ICAM1 region increases, p300 binding to this region is diminished, resulting in decreased ICAM1 expression. High NANOG expression confers PCa cells the ability to resist NK cell attack via the repression of ICAM1. Consistent with these results, low ICAM1 expression is significantly correlated with a high recurrence rate in patients with PCa.ConclusionsOur findings indicate that repression of ICAM1 is a critical mechanism by which cancer cells evade attack from NK cells during tumorigenesis. These results suggest a pivotal role of NANOG in establishing a gene expression profile for escaping the immune system.
Highlights
At the beginning of tumorigenesis, newly born cancer cells must successfully avoid attack by the immune system
Tumor formation assays of sphere-forming cancer cells were carried out using SCID or NOD/SCID mice in this experiment and in previous reports [15, 16, 26, 27]
Transplanted sphere-forming cancer cells must escape from natural killer (NK) cell attack by themselves during the initial stage before a tumor tissue-mediated immunosuppressive environment is established
Summary
At the beginning of tumorigenesis, newly born cancer cells must successfully avoid attack by the immune system. Some newly born cancer cells evade immune surveillance, defined as cancer-initiating cells (CICs), and exhibit tumorigenic potential, resulting in tumor formation. Saga et al Journal of Experimental & Clinical Cancer Research (2019) 38:416 early phase of tumorigenesis, CICs and other cancer cells derived from CICs establish a poor immunosuppressive environment due to insufficient cytokine secretion, exosome production and host-derived immunosuppressive cell attraction. These cancer cells require a distinct anticancer immune escape system to allow tumor tissue formation from the tumor tissue-mediated immunosuppressed environment. The mechanisms by which these transcription factors provide cancer cells the ability to evade anticancer immune responses remain unknown
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Experimental & Clinical Cancer Research
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
