MEDICINE AND HEALTH

The new research provides new ideas for the development of NK cell-related immunotherapies


On August 21, Cell published the latest research paper cooperated by Zhang Zemin’s research group at the Center for Biomedical Frontier Innovation (BIOPIC) of Peking University. Supported by the integration of bioinformatics data, this study systematically delineates the heterogeneity of natural killer (NK) cells between different cancer types and tissues, and discovers subclasses of NK cells with specific enrichment and abnormal killing function in the tumor microenvironment (TME), revealing the potential regulatory relationship between NK cells and other components in the microenvironment.

Key findings of the study. (Photo courtesy of the research group)

Zhang Zemin, one of the corresponding authors of the paper, told China Science News that this work innovatively integrates and uses large-scale single-cell data, reveals the shift of gene expression patterns in NK cells, captures the changes of NK cell subgroups in the tumor immune microenvironment, provides assistance for exploring new biomarkers and therapeutic targets through more comprehensive integrated analysis methods in the future, and also provides more accurate and comprehensive data support for drug development.

In recent years, empowering new technologies and interpreting complex phenomena through bioinformatics methods has become a powerful aid in exploring and solving important scientific problems.

Do different cancer types share common features of immune dysfunction? Do the same immune components function consistently across tissues and conditions? Why do different types of cancer and different patients respond differently to immunotherapy? The solution of these problems will greatly promote the development of tumor immunotherapy.

This study collected a large number of publicly available single-cell transcriptome data covering 24 cancer types, including NK cell single-cell expression profiles from 1223 samples from 716 patients and 47 healthy controls.

The researchers overcame many difficulties in data integration, including high-precision isolation of NK cells and removal of complex batch effects, and systematically identified 14 types of NK cell subsets at the pan-carcinoca level for the first time, and detailed characterization of phenotypic and functional diversity of various populations.

Based on the integrated data resources, the researchers found that the subpopulation composition of NK cells showed obvious preference among different cancer types, and the distribution of NK cell subclasses in tumors, paracancerous tissues and peripheral blood also showed obvious differences. Through bioinformatics screening such as transcriptome quantification analysis, sensitivity and specificity tests, the researchers found that RGS1 was specifically high expressed on NK cells of non-blood origin. This finding provides a new research direction for further research on tissue infiltration of NK cells, and further highlights the feasibility of studying key biological questions through integrated data analysis.

Further focusing on the tumor microenvironment, the researchers found that tumor tissues were highly enriched with a group of DNAJB1-positive NK cells. Data analysis found that this group of cells has a dysfunctional phenotype, including decreased killing, increased inhibitory receptors, and high expression of stress-related proteins, so the researchers named this group of cells tumor-associated NK cells.

Unlike the classical recognition that higher abundance of NK cells is beneficial to the survival status of tumor patients, the researchers found that the enrichment of TaNK cells was significantly associated with poor prognosis of multiple cancer types and immunotherapy resistance. These findings indicate that TaNK cells have important biological and clinical applications for follow-upThe development of NK cell-related immunotherapy methods provides new ideas.

Tang Fei, a doctoral student in the PTN program of the Institute of Advanced Interdisciplinary Studies of Peking University, and Jinhu Li, a doctoral student in the BIOPIC/School of Life Sciences, are the joint first authors of the paper, and Dongfang Wang, assistant researcher of BIOPIC, Professor Peng Hui of University of Science and Technology of China, and Zhu Linnan, associate researcher of BIOPIC are co-corresponding authors of the paper. Qi Lu, a doctoral student in Changping Laboratory, and other members of Zhang Zemin’s laboratory have made important contributions to this research. Academician Tian Zhigang of the University of Science and Technology of China provided important assistance for this research.

The research was supported by the National Natural Science Foundation of China and the Beijing Municipal Science and Technology Commission. (Source: Cui Xueqin, China Science News)

Related paper information:https://doi.org/10.1016/j.cell.2023.07.034



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