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      A new insight into tumor immune-evasion: Crosstalk between cancer stem cells and T regulatory cells

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          Abstract

          Cancer development is initiated, sustained, and aggravated by a rare population of cells, termed cancer stem cells (CSCs). Although CSCs are considered as a promising source of cells to orchestrate the immune system to work in favour of tumor, the detailed mechanisms underlying their immunomodulatory effects remain elusive. Recent reports indicate the contribution of exosomes, secreted from various cells, as mediators of cell-to-cell communication especially within the tumor microenvironment. We aimed at exploring the role of CSC-derived exosomes (CDEs) in reprogramming the host immune system by generating functional T-regulatory (Treg) cells, and at delineating the underlying mechanisms. Our results showed that CDEs play a significant role in generating CD4 +CD25 +FoxP3 + Treg cells from naive T-cells. A search for the underlying mechanism revealed the presence of FoxP3 protein in CDEs which was found to be transferred to the naïve T-cells. Exosomes from FoxP3-ablated CSCs failed to augment immuno-suppressive Treg cell generation confirming the significant role of the transported protein. In order to understand the contribution of CDE-FoxP3 in maintaining a heritably stable population of Treg cell we checked for the binding of CDE-FoxP3 on conserved non-coding sequence 2 (CNS2) region of FoxP3 promoter in T-naïve cells and found CDE-FoxP3 is indeed recruited to the CNS2 region generating stable and functionally suppressive Treg cells. These results raise the possibility that CSCs provide the initial trigger for immunosuppressive Treg cell generation and thus, breaching the deadly-liaison between them might be a promising strategy in breast cancer therapy.

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          Author and article information

          Journal
          ScienceOpen Posters
          ScienceOpen
          24 May 2020
          Affiliations
          [1 ] Division of Molecular Medicine, Bose Institute, Kolkata, India
          Article
          10.14293/S2199-1006.1.SOR-.PP22NIF.v1

          This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

          The data that support the findings of this study are available from authors but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of authors.

          Life sciences

          Cancer stem cells, Treg cells, Exosomes

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