Neutrophils are the first line of defense for innate immunityIt is widely involved in important processes such as tumor immune circulation, immune editing, and immune escape。At the same time, neutrophils are the most abundant type of white blood cells in the human body, accounting for 40% to 70% of human white blood cells and are an important component of the tumor microenvironment。However, neutrophils have a short half-life (6-8 hours) and fragile cellsThese difficulties have led to few large-scale systematic studies of neutrophils, whether they exert anti-tumor or pro-tumor functionsIt is the focus of controversy in the field. In recent years, research on tumor microenvironment at the pan-cancer scale has been in full swingThis strategy opens up new opportunities for systematic study of neutrophil function and phenotype. On March 5, 2024, Zhongshan Hospital affiliated to Fudan UniversityFan JiaAcademician andHigh strengthProfessor, Shanghai Institute of Immunology and Infection, Chinese Academy of SciencesZhang XiaomingResearcher, Institute of Biomedical Sciences, Fudan UniversityYang LiFellows collaborate oncellpublished a post entitledneutrophil profiling illuminates anti-tumor antigen-presenting potencyResearch**,Using self-test data (79.)29%) and public data (2071%), based on the neutrophil single-cell transcriptome of 143 patients with a total of 225 samples from 17 cancer types, including liver cancer, cholangiocarcinoma, and gallbladder cancer, systematically revealed the phenotypic diversity and plasticity of human tumor-associated neutrophils(e.g., antigen-presenting type, pro-angiogenesis type, inflammatory type, etc.).It was found that HLA-DR+CD74+ neutrophils were positively correlated with the prognosis of patients in multiple cancer types, which could induce T-cell antigen-specific responses and promote the formation of a "hot tumor" microenvironment, which could be used as a potential immuno-sensitization strategy. 
In this study, the researchers integrated neutrophil single-cell transcriptome data from 225 patient samples and found that neutrophils could be divided into 10 large groups, such as HLA-DR+CD74+ antigen-presenting neutrophils, VEGFA+SPP1+ pro-angiogenesis neutrophils, and CXCL8+IL1B+ inflammatory types, which correspond to different immunophenotypes, chemokine characteristics, and maturation states. In multiple cancer types, HLA-DR+CD74+ neutrophils were associated with a better prognosis, while VEGFA+SPP1+ neutrophils were associated with a worse prognosis. The researchers characterized the different maturation states of neutrophils by comprehensively using four single-cell trajectory algorithms, multiple immunofluorescence, flow cytometry and other technologies, and found that HLA-DR+CD74+ neutrophils may be in a mature state of terminal differentiation, suggesting the important role of this subpopulation. Therefore, the researchers further focused on the function and regulatory mechanism of HLA-DR+CD74+ neutrophils, and found the potential relationship between leucine metabolism and neutrophil antigen presentation function through single-cell metabolic pathway analysis and small-scale metabolite in vitro screening: leucine can up-regulate the expression of MHC-II antigen-presenting molecule HLA-DR and related costimulatory molecules in neutrophils. The authors further found that leucine can be remodeled through mitochondrial structure and function, and enhance acetyl-CoA production, up-regulate the acetylation modification of H3K27 in the promoter region of MHC-II molecules, thereby up-regulating antigen-presenting molecules such as HLA-DR. In order to further study the antigen-presenting function of this group of cells, the authors found that HLA-DR+CD74+ neutrophils can present tumor neoantigens to T cells, reshape the T cell immune repertoire and enhance antigen-specific responses. These results suggest the metabolic plasticity and value of HLA-DR+CD74+ neutrophils. On this basis, the authors explored the anti-tumor value of antigen-presenting neutrophils. Neutrophil subsets associated with CD74+ antigen presentation were also found in several types of mouse tumors. In mouse models, leucine-rich diets or CD74+ neutrophil adoptive** enhanced anti-PD-1 immunity**. However, when the antigen was presented to neutrophil adoptive treatment of patients' ** tumor fragments (PDTFS), the antigen-specific reactive molecules and killer molecules of T cells were significantly increased. In addition, based on the analysis of immunosequencing data of tumor patients, it was found that there was a significant positive correlation between antigen presentation of neutrophils and the degree of immune** response. To sum up,This work generated neutrophil transcriptome data of multiple cancer species, deeply analyzed the transcriptional patterns, cell states, metabolic characteristics, and clinical relevance of neutrophil cancer species, focused on the antigen presentation function of HLA-DR+CD74+ neutrophils, and explored the possibility of using neutrophil antigen presentation to sensitize immunity**. 
Figure 1Schematic diagram of the study design. Academician Fan Jia and Professor Gao Qiang from Zhongshan Hospital affiliated to Fudan University, researcher Zhang Xiaoming from the Shanghai Institute of Immunology and Infection, Chinese Academy of Sciences, and researcher Yang Li from the Institute of Biomedical Sciences of Fudan University are the corresponding authors of this paper. Fudan University doctoral students Wu Yingcheng, Ma Jiaqiang, Yang Xupeng, postdoctoral student Nan Fang, and master's student Zhang Tian became the co-first authors. This study was supported by Prof. Qunying Lei and Prof. Di Zhu from Fudan University, Prof. Xiuxuan Zhu from Massachusetts General School of Harvard University, Prof. Claude Leclerc from Institut Pasteur in France, and Prof. Feng Wang and Prof. Jing Wang from the Institute of Immunology of Shanghai Jiao Tong University. Professor Gao Qiang of Fudan University is looking for postdoctoral fellows (see Bioart Talents: Professor Gao Qiang's research group of Fudan University is recruiting postdoctoral fellows for details). Professor Gao Qiang is the winner of the National High-level Talent Program, the National Ten Thousand Talents Program, the National Excellent Youth, the assistant to the president of Zhongshan Hospital affiliated to Fudan University, the deputy director of the Department of Liver Surgery, the chief physician, the professor, the doctoral supervisor, and the Institute of Biomedical Sciences and the Institute of Phenotyping of Fudan University. The annual salary of the postdoctoral fellows before tax is 300,000 yuan, and they will enjoy the scientific research performance rewards of our institute during the employment period, and those with outstanding work will be treated preferentially, given additional subsidies and allowances, and will be provided with jobs after leaving the station. Resume delivery(If you are interested, please send your resume and other materials to):Original link:
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