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## Meet the editor

Professor Leisheng Zhang is a cell biologist and the leader of a research team devoted to tissue engineering and regenerative medicine. In 2012, he obtained a BVetMed from Jilin University, China. In 2018, he obtained a Ph.D. in Cellular Biology from the Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC) and Tsinghua University, China. In 2019 and 2022, Dr. Zhang conducted post-doctoral

research at the Nankai University School of Medicine and the Chinese Academy of Sciences (CAS). He has worked on projects for the National Natural Science Foundation of China and has published more than sixty articles, thirteen books, and more than thirty patents.

### Contents


## Preface

Natural killer (NK) cells, also known as innate lymphoid cells (ILCs), belong to ILCs with broad distributions in the body. NK cells encompass distinct populations based on CD56 intensity in humans and CD11b and CD27 expression in mice. NK cells are unique immune cells that are capable of efficient killing of transformed and infected cells as well as pathogenic microorganisms and tumor cells. As such, autologous and allogeneic NK cells have advantages in cancer immunotherapy, delaying aging, and eradicating pathogenic infections.

For decades, investigators in the field have identified NK cells from a variety of sources, such as peripheral blood, umbilical cord blood, placental blood, NK cell lines, and even stem cells. Of these, perinatal blood-derived NK cells have proven to exhibit robust ex vivo expansion activity and thus have greater potential for use in cancer immunosurveillance and immunotherapy compared to their counterparts. Currently, NK cell-based immunotherapy has been demonstrated to be safe and effective for treating cancers including hematologic malignancies and metastatic solid tumors via antibody-dependent cell-mediated cytotoxicity (ADCC), granule enzymes, and perforin dispenses with pre-sensitization and antigen presentation. The effectiveness of NK cells in the elimination and surveillance of cancers has fascinated immunologists for decades.

This book discusses NK cell-based cytotherapy and highlights NK cells as essential components of the innate immune system and tumor immune surveillance. Distinct from chimeric antigen receptor-transduced T (CAR-T) cells, NK cells or CAR-transduced NK (CAR-NK) cells are exempt from untoward effects such as neurotoxicity, cytokine storm syndrome (CSS), and graft-versus-host disease (GvHD). As a pivotal part of the innate immune system, NK cells have been recognized as an attractive option for cancer immunotherapy due to their ability to kill cancer cells or infected cells without prior sensitization. Collectively, NK cells are unique cell sources with anti-neoplastic, anti-infectious, and immunomodulatory effects based on both direct cellular cytotoxicity and cytokine production that is not major histocompatibility complex (MHC) restricted. It is noteworthy that NK cells have been reported with the capability of killing tumor cells autonomously in the tumor microenvironment, which thus represents the unique effect against immune escape, tumor progression, and metastasis. Overall, this book highlights the feasibility of NK cell-based cytotherapy for cancer immunotherapy and the promising prospects of NK cells or CAR-NK cells in regenerative medicine in the future, which will benefit the development of cancer immunosurveillance and cancer immunotherapy.

**1**

Section 1

The Landscape of Natural

Killer Cells

Section 1
