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Tseng HC, Bui V, Man YG, et al. Induction of Split Anergy Conditions Natural Killer Cells to Promote Differentiation of Stem Cells through Cell-Cell Contact and Secreted Factors. Front Immunol. 2014;5:269doi: 10.3389/fimmu.2014.00269.
Tseng, H. C., Bui, V., Man, Y. G., Cacalano, N., & Jewett, A. (2014). Induction of Split Anergy Conditions Natural Killer Cells to Promote Differentiation of Stem Cells through Cell-Cell Contact and Secreted Factors. Frontiers in immunology, 5269. https://doi.org/10.3389/fimmu.2014.00269
Tseng, Han-Ching, et al. "Induction of Split Anergy Conditions Natural Killer Cells to Promote Differentiation of Stem Cells through Cell-Cell Contact and Secreted Factors." Frontiers in immunology vol. 5 (2014): 269. doi: https://doi.org/10.3389/fimmu.2014.00269
Tseng HC, Bui V, Man YG, Cacalano N, Jewett A. Induction of Split Anergy Conditions Natural Killer Cells to Promote Differentiation of Stem Cells through Cell-Cell Contact and Secreted Factors. Front Immunol. 2014 Jun 19;5:269. doi: 10.3389/fimmu.2014.00269. eCollection 2014. PMID: 24995006; PMCID: PMC4062968.
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Front Immunol. 2014 Jun 19;5:269. doi: 10.3389/fimmu.2014.00269. eCollection 2014.

Induction of Split Anergy Conditions Natural Killer Cells to Promote Differentiation of Stem Cells through Cell-Cell Contact and Secreted Factors.

Frontiers in immunology

Han-Ching Tseng, Vickie Bui, Yan-Gao Man, Nicholas Cacalano, Anahid Jewett

Affiliations

  1. Division of Oral Biology and Oral Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology , Los Angeles, CA , USA.
  2. Bon Secours Cancer Institute, Bon Secours Health System , Richmond, VA , USA.
  3. Department of Radiation Oncology, University of California Los Angeles School of Medicine , Los Angeles, CA , USA.
  4. Division of Oral Biology and Oral Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology , Los Angeles, CA , USA ; The Jonsson Comprehensive Cancer Center, University of California Los Angeles School of Dentistry and Medicine , Los Angeles, CA , USA.

PMID: 24995006 PMCID: PMC4062968 DOI: 10.3389/fimmu.2014.00269

Abstract

In this paper, we provide evidence that anergized NK cells through secreted factors and direct cell-cell contact have the ability to induce differentiation of healthy dental pulp stem cells and stem cell of apical papillae as well as transformed oral squamous cancer stem cell (OSCSC) and Mia-Paca-2, poorly differentiated stem-like pancreatic tumors, resulting in their resistance to NK cell-mediated cytotoxicity. Induction of NK cell resistance and differentiation in the stem cells correlated with the increased expression of CD54, B7H1, and MHC class I, and mediated by the combination of membrane-bound or secreted IFN-γ and TNF-α from the NK cells since antibodies to both cytokines and not each one alone were able to inhibit differentiation or resistance to NK cells. Similarly, antibodies to both TNF-α and IFN-γ were required to prevent NK-mediated inhibition of cell growth, and restored the numbers of the stem cells to the levels obtained when stem cells were cultured in the absence of anergized NK cells. Interestingly, the effect of anti-IFN-γ antibody in the absence of anti-TNF-α antibody was more dominant for the prevention of increase in surface receptor expression since its addition abrogated the increase in CD54, B7H1, and MHC class I surface expression. Antibodies to CD54 or LFA-1 was unable to inhibit differentiation whereas antibodies to MHC class I but not B7H1 increased cytotoxicity of well-differentiated oral squamous carcinoma cells as well as OSCSCs differentiated by the IL-2 + anti-CD16 mAb-treated NK cells whereas it inhibited the cytotoxicity of NK cells against OSCSCs. Thus, NK cells may inhibit the progression of cancer by killing and/or differentiation of cancer stem cells, which severely halt cancer growth, invasion, and metastasis.

Keywords: IFN-γ; MP2; NK; OSCCs; OSCSCs; cytotoxicity; regulatory NK

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