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Drawing the molecular roadmap of Human Natural Killer Cell development

AI generated artwork representing natural killer cell development. Graphical image.
Researchers studying natural killer cells present a comprehensive map of how these cells develop in humans, detailing their regulatory networks along the way. Image credit: AI-illustrated artwork via Midjourney // Dang Nghiem Vo

At any given time, more than 2 billion natural killer cells patrol the adult bloodstream as frontline defenders, protecting against infections and cancer. In a recent study published in Blood Advances, researchers at Lund University's Lund Stem Cell Center present a comprehensive developmental map of human NK cells and their regulatory networks.

Natural killer (NK) cells, named for their rapid response to threats, are key components of a healthy immune system. Constantly scanning the body for signs of trouble, they quickly destroy cancer and virus-infected cells. Yet, despite their importance, the stages of human NK cell development have long been poorly understood, with previous studies often relying on animal models.

"Even nearly fifty years from their discovery, and twenty years after introduction to the clinic, our collective understanding of human NK cell development was fragmented, based on snapshots, so that it was like trying to solve a puzzle without seeing the whole picture," explains Ewa Sitnicka Quinn, professor at Lund University and leader of the Lymphoid Development and Regulation research group at Lund Stem Cell Center.

Understanding Human NK Cell Development

To gain deeper insights into this process, the researchers devised a new dynamic model system using stem cells from human umbilical cord blood and a cellular environment built by mouse stroma cells, supplemented with required nutrients and growth factors. This approach allowed them to observe over time the birth and maturation of NK cells in a controlled laboratory setting.

Portrait of Dang (right) and Ewa (left). Photo.
Researchers Ewa Sitnicka Quinn (left) and Dang Nghiem Vo (right).

"We found that our model accurately mimics both the function and gene profile of NK cells found in human bone marrow and the lymphoid tissues, key areas where these cells develop and mature in the human body, providing a reliable platform for future studies," highlights Dang Nghiem Vo, researcher at Lund Stem Cell Center and lead author of the study.

Using advanced techniques like clonal tracing and DNA barcoding, the team pieced together a detailed "cellular atlas" of NK cell development and maturation, described by Ewa Sitnicka Quinn as a roadmap, outlining the developmental stages and decision points in the growth of NK cells.

"This atlas is already proving valuable in identifying key pathways and interactions among NK cells and other cells of the immune system," adds Dang Nghiem Vo. "For instance, we uncovered a cluster or network of genes that work together to enhance NK cells' ability to target infected or cancerous cells."

Future Directions in NK Cell Research

NK cell therapy, a form of cellular immunotherapy, uses NK cells to detect and destroy abnormal cells in the body, including cancer. These cells offer advantages over traditional treatments like chemotherapy, with high specificity and fewer side effects. With the growing recognition of the benefits of NK cell therapies, the focus is now on optimizing the cultivation of these cells in the lab for improved cancer treatments. 

"The success of NK cell therapies largely depends on having an abundant supply of cells, similar to the demands of stem cell therapies using hematopoietic stem cells. This underscores the urgency of developing more effective techniques for NK cell expansion," elaborates Ewa Sitnicka Quinn.

With this new developmental roadmap, researchers are ready to explore the healthy development of NK cells and the underlying causes of NK cell dysfunction in various diseases. "With a clearer understanding of these malfunctions, researchers can pursue targeted therapies to correct them," concludes Dang Nghiem Vo, hinting at the promising future of immunotherapy research.

Dang Nghiem Vo, is a postdoctoral researcher in the Lymphoid Development and Regulation and Bone Marrow (Stromal) Stem Cells and Cellular Therapies research groups at Lund Stem Cell Center.

Profile in Lund University research portal

Ewa Sitnicka Quinn, is a Professor in the Division of Molecular Hematology at the Faculty of Medicine and Principal Investigator at Lund Stem Cell Center and the Lund University Cancer Cancer.

Profile in Lund University research portal

About the study:


A temporal developmental map separates Human NK Cells from Non-toxic ILCs through clonal and single-cell analysis

Blood Advances, online 14 Mar. 2024. 


The study is financed with the support of the Swedish Cancer Society, the Swedish Research Council, the Alfred Österlunds Foundations, and the Fysiografiska Foundation

Brief facts about the study
hematopoiesis // stem cells // natural killer cells // experimental research // immunology // in vitro