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- W2322496617 abstract "Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide. There is little therapy for advanced disease and recurrence rates can be as high as 50% following resection. Evidence in several tumor types suggests that cancer stem cells (CSCs) contribute to tumorigenicity, therapeutic resistance and recurrence, however the HCC CSC phenotype remains to be completely defined. HCC recurrence is influenced by the degree of immune response in the tumor microenvironment. Therefore, we aimed to characterize HCC-CSCs phenotype and investigate the interaction between CSCs and immune cell subsets. To identify a dominant CSC population in HCC, we examined several putative CSC markers, including CD44, CD90, CD133 and EpCAM on primary human resected HCCs (n=6), HCC xenografts (n=2), and HCC cell lines (n=3) using flow cytometry. Cells from all sources consistently showed discrete populations of CD44 + cells (2-40%), while other common CSC markers showed significant heterogeneity. CD44 + cells isolated from HCC xenografts or HepG2 cells by fluorescence-activated cell sorting (FACS) demonstrated enhanced tumorigenic potential with as little as 100 cells implanted into NOD-SCID/IL-2Rg null mice compared to no tumor from 100 CD44 − cells. CD44 + cells were also able to produce heterogenic tumor mass in vivo. Moreover, CD44 + cells demonstrated increased sphere forming capacity in serum free media (2 fold, p + HCC cells were resistant to effector cytokines such as IFNγ and TNFα and effector responses during co-culture with anti-CD3/anti-CD28 activated T cells from healthy donor PBMCs. CD44 + HCC cells had 2-fold increased expression of B7-H1, a co-inhibitory molecule for T cells, when compared to non-CSCs during exposure to activated T cells or effector cytokine IFNγ, suggesting a possible mechanism of resistance to immune effectors in the HCC microenvironment. In conclusion, CD44 discriminates for the HCC CSC as evidenced by CD44 + subset demonstrating enhanced tumorigenicity, sphere forming capacity and resistance to chemotherapeutic agents. CD44 + CSC are also resistant to activated T cells and effector cytokines suggesting that microenvironmental factors related to immune response may be important for HCC recurrence or progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2450. doi:10.1158/1538-7445.AM2011-2450" @default.
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- W2322496617 date "2011-04-15" @default.
- W2322496617 modified "2023-09-27" @default.
- W2322496617 title "Abstract 2450: Resistance of CD44+hepatocellular carcinoma cancer stem cellsto immune effector responses" @default.
- W2322496617 doi "https://doi.org/10.1158/1538-7445.am2011-2450" @default.
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