Natural Killer (NK) cells, a category of white blood cells, are integral to the body’s immune system. These cells are unique in that they are capable of identifying and eradicating cells compromised by viral infections or cancer, without needing previous exposure to the target cell. This attribute positions them as an essential initial safeguard against novel health threats.
A collaborative research initiative led by Prof. Tian Zhigang and Prof. Peng Hui from the University of Science and Technology of China (USTC), affiliated with the Chinese Academy of Sciences (CAS), in conjunction with Prof. Zhang Zemin from Peking University, has elucidated the diversity in natural killer (NK) cells across various forms of cancer and bodily tissues. The scientists discovered an atypical subset of NK cells with irregular anti-tumor functionality, localized predominantly in the tumor microenvironment. These discoveries were disseminated in a recent edition of the scientific journal Cell.
Recognized for their capability to effectively neutralize cancer cells, NK cells have risen to prominence in the sphere of immunotherapy, particularly showing promise in the treatment of hematological malignancies. Nevertheless, the complex variability of NK cells—manifesting as differences in phenotype and function within specific tissue microenvironments—creates obstacles for their broader application in the therapy of solid tumors.
Over a prolonged period, the team under Prof. Tian and Prof. Peng has investigated the complex heterogeneity of NK cells across different bodily tissues. In this particular research endeavor, they amassed a comprehensive dataset consisting of single-cell transcriptomes, which covered 24 types of cancer and included a total of 1,223 samples from 716 patients and 47 healthy subjects. They categorized five unique subsets of CD56brightCD16lo NK cells and nine distinct subsets of CD56dimCD16hi NK cells, thoroughly examining their phenotypic and functional variance at an all-encompassing pan-cancer scale.
By analyzing this extensive dataset, the researchers identified a predilection for specific NK cell subtypes in different forms of cancer. They also observed notable discrepancies in the distribution of NK cell subtypes within tumors, adjacent tissues, and peripheral blood. Utilizing sophisticated bioinformatics methodologies, the gene RGS1 was identified as being especially prominent in non-blood NK cells. At the transcriptome level, RGS1 exhibited noteworthy specificity and sensitivity when compared to standard tissue residency markers.
Further scrutiny of the tumor microenvironment disclosed that a cluster of DNAJB1+CD56dimCD16hi NK cells were considerably concentrated in tumor tissues. Evaluation of this subset uncovered a dysfunctional phenotype characterized by diminished cytotoxicity, augmented inhibitory receptors, and elevated stress-related protein levels. This newly identified subtype, termed “Tumor-associated NK cells” (TaNK cells), contradicted the prevailing wisdom that increased NK cell presence is favorable for cancer patients. Contrarily, TaNK cells were strongly linked to negative outcomes across diverse cancer types and showed significant resistance to immunotherapy treatments.
In addition, the research team ascertained that LAMP3+ dendritic cells (DCs) are pivotal modulators of NK cell functionality. Spatial distribution data indicated that NK cells in immediate vicinity to LAMP3+ DCs displayed reduced cytotoxic capabilities, suggesting that LAMP3+ DCs may exert an aberrant regulatory influence on NK cell functionality within the tumor microenvironment.
Reference: “A pan-cancer single-cell panorama of human natural killer cells” by Fei Tang, Jinhu Li, Lu Qi, Dongfang Liu, Yufei Bo, Shishang Qin, Yuhui Miao, Kezhuo Yu, Wenhong Hou, Jianan Li, Jirun Peng, Zhigang Tian, Linnan Zhu, Hui Peng, Dongfang Wang and Zemin Zhang, published on 21 August 2023 in Cell.
DOI: 10.1016/j.cell.2023.07.034
Table of Contents
Frequently Asked Questions (FAQs) about Tumor-associated NK cells
What are Natural Killer (NK) cells and why are they important?
Natural Killer (NK) cells are a type of white blood cell that plays a significant role in the body’s immune system. They are unique because they can identify and eliminate cells that are infected by viruses or have turned cancerous without prior exposure to the target cell. This makes them a crucial first line of defense against new health threats.
Who led the research on the unusual subtype of NK cells?
The research was spearheaded by a team from the University of Science and Technology of China (USTC), affiliated with the Chinese Academy of Sciences (CAS), in collaboration with Prof. Zhang Zemin from Peking University.
What was the main finding of this research?
The main discovery was the identification of an atypical subset of NK cells that exhibit abnormal anti-tumor functions. These cells, referred to as “Tumor-associated NK cells” or TaNK cells, are predominantly found within the tumor microenvironment and show significant resistance to immunotherapy.
What challenges do these Tumor-associated NK cells pose?
These TaNK cells contradict the traditional understanding that higher NK cell abundance is beneficial for cancer patients. They are associated with adverse prognoses across different cancer types and show a considerable resistance to immunotherapeutic treatments.
What methodology did the researchers use?
The researchers employed a comprehensive dataset of single-cell transcriptomes, covering 24 types of cancer and 1,223 samples from 716 patients and 47 healthy individuals. Advanced bioinformatics techniques were utilized to dissect the phenotypic and functional diversity of NK cells.
What role do LAMP3+ dendritic cells (DCs) play according to the research?
According to the study, LAMP3+ dendritic cells are critical regulators of NK cell functionality. These cells appear to exert an abnormal regulatory influence on NK cell functionality within the tumor microenvironment, leading to reduced cytotoxic capabilities.
Where was the research published and what is the DOI?
The research findings were published in the scientific journal Cell on 21 August 2023. The DOI for the paper is 10.1016/j.cell.2023.07.034.
More about Tumor-associated NK cells
- Research Article in Cell – The original research paper detailing the findings of the unusual subset of NK cells.
- University of Science and Technology of China (USTC) – The institution where the research was conducted.
- Chinese Academy of Sciences (CAS) – The organization affiliated with the research team.
- Peking University
5 comments
LAMP3+ DCs messing up NK cells? Not cool, man. Gotta fix that!
taNK cells? weird name, but sounds like bad news for cancer peeps. no good.
oh, so NK cells are big deal in immune sys. important stuff!
Where can I read more? Got a link?
whoa, that’s some sci stuff right there. Fancy terms and all.