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Microbes & Immunity

REVIEW ARTICLE
iPSC-mediated genetic manipulation

promotes natural killer cell-centered cancer
immunotherapy

1†
2
3
1†
Yiran Zheng , Yumo Zhang , Zhouxin Yang *, Wing Keung Chan , and
1
Youwei Wang *
1 Institute of Medical Engineering and Translational Medicine, Medical College, Tianjin University,
Tianjin, China
2 Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Zhejiang
Hospital, Hangzhou, China
3 Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus,
Ohio, United States of America

Abstract
Natural killer (NK) cells demonstrate potent cytotoxic activities and the capacity to
secrete cytokines. Their distinctive capability to trigger cell death, bypassing the need
† These authors contributed equally for major histocompatibility complex recognition, opens promising avenues for their
to this work. use in clinical settings such as allogeneic transplantation and tumor immunotherapy.
*Corresponding authors: Although the ability of NK cells to kill hematological tumors has been widely
Zhouxin Yang recognized, their effectiveness in treating solid tumors is not as pronounced. The
(yangzhouxin@hotmail.com);
Youwei Wang intricate interplay of NK cells with the tumor microenvironment, specifically in the
(youwei.wang@tju.edu.cn) context of solid malignancies, has been noted to attenuate the anti-cancer prowess
of NK cells and foster the ability of malignant cells to elude immune surveillance.
Citation: Zheng Y, Zhang Y,
Yang Z, Chan WK, Wang Y. iPSC- Successful NK cell-centered immunotherapy hinges on obtaining a substantial
mediated genetic manipulation quantity of NK cells with potent tumor-killing capabilities. However, the current
promotes natural killer cell-centered challenge lies in the limited ex vivo expansion of NK cells and the inefficiency of gene
cancer immunotherapy. Microbes &
Immunity. 2025;2(1):27-44. introduction methods. Induced pluripotent stem cells (iPSCs) are multipotent stem
doi: 10.36922/mi.5653 cells with relatively easier gene transfection capability and theoretically unlimited
Received: October 28, 2024 proliferation potential. NK cells derived from iPSCs circumvent the challenge of
difficult genetic modification in NK cells, offering various potential strategies to
Revised: November 27, 2024 counteract the immune suppression induced by the tumor microenvironment.
Accepted: December 5, 2024
Published Online: December 31, Keywords: Induced pluripotent stem cells; Natural killer cells; Solid cancer; CAR-NK cells;
2024
Immunotherapy
Copyright: © 2024 Author(s).
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution, 1. Introduction
and reproduction in any medium,
provided the original work is Innate lymphoid cells (ILCs) are classified into three principal groups: Group 1, Group 2,
properly cited. and Group 3 ILCs. Natural killer (NK) cells are categorized within Group 1 ILCs, along
1
Publisher’s Note: AccScience with ILC1. Each of these groups has a corresponding counterpart in adaptive immunity
Publishing remains neutral with characterized by T helper (Th) cells: Th1 for Group 1, Th2 for Group 2, and Th17 for
regard to jurisdictional claims in 2
published maps and institutional Group 3, reflecting their roles and functions in the immune response. NK cells, first
affiliations. identified in the 1970s, derive their name from their innate ability to kill target cells

Volume 2 Issue 1 (2025) 27 doi: 10.36922/mi.5653