Defective Patient NK Function Is Reversed by AJ2 Probiotic Bacteria or Addition of Allogeneic Healthy Monocytes

Meng-Wei Ko; Kawaljit Kaur; Tahmineh Safaei; Wuyang Chen; Christine Sutanto; Paul Wong; Anahid Jewett

doi:10.3390/cells11040697

Defective Patient NK Function Is Reversed by AJ2 Probiotic Bacteria or Addition of Allogeneic Healthy Monocytes

Cells. 2022 Feb 16;11(4):697. doi: 10.3390/cells11040697.

Authors

Meng-Wei Ko¹, Kawaljit Kaur¹, Tahmineh Safaei¹, Wuyang Chen¹, Christine Sutanto¹, Paul Wong¹, Anahid Jewett^{1

2}

Affiliations

¹ The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles, Los Angeles, CA 90095, USA.
² The Jonsson Comprehensive Cancer Center, UCLA School of Dentistry and Medicine, Los Angeles, CA 90095, USA.

Abstract

In this paper, we present the role of autologous and allogeneic monocytes from healthy individuals and those of the cancer patients, with a number of distinct cancers, in activating the function of natural killer (NK) cells, in particular, in induction of IFN-γ secretion by the NK cells and the functional capability of secreted IFN-γ in driving differentiation of the tumor cells. In addition, we compared the roles of CD16 signaling as well as sonicated probiotic bacteria AJ2 (sAJ2)-mediated induction and function of IFN-γ-mediated differentiation in tumor cells. We found that monocytes from cancer patients had lower capability to induce functional IFN-γ secretion by the autologous CD16 mAb-treated NK cells in comparison to those from healthy individuals. In addition, when patient monocytes were cultured with NK cells from healthy individuals, they had lower capability to induce functional IFN-γ secretion by the NK cells when compared to those from autologous monocyte/NK cultures from healthy individuals. Activation by sAJ2 or addition of monocytes from healthy individuals to patient NK cells increased the secretion of functional IFN-γ by the NK cells and elevated its functional capability to differentiate tumors. Monocytes from cancer patients were found to express lower CD16 receptors, providing a potential mechanism for their lack of ability to trigger secretion of functional IFN-γ. In addition to in vitro studies, we also conducted in vivo studies in which cancer patients were given oral supplementation of AJ2 and the function of NK cells were studied. Oral ingestion of AJ2 improved the secretion of IFN-γ by patient derived NK cells and resulted in the better functioning of NK cells in cancer patients. Thus, our studies indicate that for successful NK cell immunotherapy, not only the defect in NK cells but also those in monocytes should be corrected. In this regard, AJ2 probiotic bacteria may serve to provide a potential adjunct treatment strategy.

Keywords: AJ2; CD16 receptor; IFN-γ; NK cells; differentiation; monocytes.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Bacteria
Hematopoietic Stem Cell Transplantation*
Humans
Killer Cells, Natural
Monocytes
Probiotics* / pharmacology

Grants and funding

R01 DE012880/DE/NIDCR NIH HHS/United States