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Innovation point: The research group of the National Engineering Research Center for Immunobiological Products has discovered a new subset of FasL+ PD-L2+ immunosuppressive neutrophils in the gastric cancer microenvironment, revealing its inducing regulatory mechanism and immunopathological effect mechanism, providing new insights for gastric cancer immune intervention.
target
.
Key words: gastric cancer, neutrophils, immunosuppression, National Research Center for Immunobiologics Engineering Technology Gastric cancer is one of the most common malignant tumors, and its lethality ranks second in the world
.
China is a country with a high incidence of gastric cancer.
At present, gastric cancer ranks among the top three malignant tumors in China in terms of incidence and death, and has become an important killer that threatens national health
.
Tumor immunity has always been accompanied by the occurrence, development and prognosis of gastric cancer, and the cellular immune response in the tumor microenvironment of patients with gastric cancer has its unique network regulation characteristics, which has always been a research hotspot in this field
.
Tumor cells and infiltrating immune cells in the interstitium jointly "shape" the tumor microenvironment; among them, neutrophils, as innate immune cells, infiltrate in large numbers in the tumor microenvironment, and can play a role in the "tumor killer"-CD8+ Immunomodulatory effects of T lymphocytes
.
However, the intrinsic effector mechanisms and functional subpopulations of gastric cancer-associated neutrophils on CD8+ T lymphocyte immune regulation remain unclear
.
In response to this problem, the Manor research group of the National Research Center for Immunobiological Products Engineering and Technology conducted research using human clinical samples: gastric cancer-related neutrophils mediate their infiltration in the gastric cancer microenvironment through the CXCL12-CXCR4 mechanism; In tumor tissue, more than 20% of gastric cancer-associated neutrophils exhibited a "dual" phenotype of FasL+PD-L2+
.
At the same time, this FasL+ PD-L2+ neutrophil subset mainly relies on the immunosuppressive molecules FasL and PD-L2 to exert the anti-tumor effect of inhibiting CD8+ T lymphocytes, thereby mediating the formation of the immunosuppressive pathological microenvironment of gastric cancer
.
Further mechanism studies revealed that Th17 cells and gastric cancer tumor cells in the gastric cancer microenvironment secrete IL-17A and G-CSF, respectively, which in turn activate the ERK-NF-κB and JAK-STAT3 pathways, and induce the regulation of gastric cancer-associated neutrophils to express FasL and G-CSF.
PD-L2
.
The results were published in Advanced Science
.
The results of this study have important potential implications for clinical immune intervention
.
In gastric cancer immunotherapy, the immunosuppressive molecules FasL and PD-L2 can be selected as direct targets, or the upstream regulators IL-17A and G-CSF can be selected as indirect targets, which actually provides a pathological Novel therapeutic ideas for neutrophil subset-related regulatory effector pathways
.
At the same time, FasL+ PD-L2+ neutrophil subsets can also be used as a new indicator for monitoring the tumor microenvironment, to judge the state of the tumor microenvironment by its response level, and then to preoperative adjustment, regimen selection and surgical treatment of gastric cancer immunotherapy.
Post-treatment guidance
.
WILEY Paper Information: FasL+ PD-L2+ Identifies a Novel Immunosuppressive Neutrophil Population in Human Gastric Cancer That Promotes Disease ProgressionZhiguo Shan, Yongliang Zhao, Jinyu Zhang, Zongbao Yan, Tingting Wang, Fangyuan Mao, Yongsheng Teng, Liusheng Peng, Wanyan Chen, Pan Wang , Ping Cheng, Wenqing Tian, Jun Chen, Weisan Chen, Yuan Zhuang*Advanced ScienceDOI: 10.
1002/advs.
202103543Click "Read the original text" in the lower left corner to view the original text of the paper
.
Introduction to AdvancedScience Journal Advanced Science is a high-quality open-source journal founded by Wiley in 2014.
It publishes innovative achievements and cutting-edge progress in various fields such as materials science, physical chemistry, biomedicine, and engineering
.
The journal is committed to maximizing the dissemination of scientific research to the public, and all articles are freely available
.
The latest impact factor is 16.
806, and the 2020 SCI journals of the Chinese Academy of Sciences are divided into the Q1 area of materials science and the Q1 area of engineering technology
.
Press and hold the QR code on the official WeChat platform of AdvancedScienceNewsWiley's scientific research information to follow us and share cutting-edge information｜Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com
target
.
Key words: gastric cancer, neutrophils, immunosuppression, National Research Center for Immunobiologics Engineering Technology Gastric cancer is one of the most common malignant tumors, and its lethality ranks second in the world
.
China is a country with a high incidence of gastric cancer.
At present, gastric cancer ranks among the top three malignant tumors in China in terms of incidence and death, and has become an important killer that threatens national health
.
Tumor immunity has always been accompanied by the occurrence, development and prognosis of gastric cancer, and the cellular immune response in the tumor microenvironment of patients with gastric cancer has its unique network regulation characteristics, which has always been a research hotspot in this field
.
Tumor cells and infiltrating immune cells in the interstitium jointly "shape" the tumor microenvironment; among them, neutrophils, as innate immune cells, infiltrate in large numbers in the tumor microenvironment, and can play a role in the "tumor killer"-CD8+ Immunomodulatory effects of T lymphocytes
.
However, the intrinsic effector mechanisms and functional subpopulations of gastric cancer-associated neutrophils on CD8+ T lymphocyte immune regulation remain unclear
.
In response to this problem, the Manor research group of the National Research Center for Immunobiological Products Engineering and Technology conducted research using human clinical samples: gastric cancer-related neutrophils mediate their infiltration in the gastric cancer microenvironment through the CXCL12-CXCR4 mechanism; In tumor tissue, more than 20% of gastric cancer-associated neutrophils exhibited a "dual" phenotype of FasL+PD-L2+
.
At the same time, this FasL+ PD-L2+ neutrophil subset mainly relies on the immunosuppressive molecules FasL and PD-L2 to exert the anti-tumor effect of inhibiting CD8+ T lymphocytes, thereby mediating the formation of the immunosuppressive pathological microenvironment of gastric cancer
.
Further mechanism studies revealed that Th17 cells and gastric cancer tumor cells in the gastric cancer microenvironment secrete IL-17A and G-CSF, respectively, which in turn activate the ERK-NF-κB and JAK-STAT3 pathways, and induce the regulation of gastric cancer-associated neutrophils to express FasL and G-CSF.
PD-L2
.
The results were published in Advanced Science
.
The results of this study have important potential implications for clinical immune intervention
.
In gastric cancer immunotherapy, the immunosuppressive molecules FasL and PD-L2 can be selected as direct targets, or the upstream regulators IL-17A and G-CSF can be selected as indirect targets, which actually provides a pathological Novel therapeutic ideas for neutrophil subset-related regulatory effector pathways
.
At the same time, FasL+ PD-L2+ neutrophil subsets can also be used as a new indicator for monitoring the tumor microenvironment, to judge the state of the tumor microenvironment by its response level, and then to preoperative adjustment, regimen selection and surgical treatment of gastric cancer immunotherapy.
Post-treatment guidance
.
WILEY Paper Information: FasL+ PD-L2+ Identifies a Novel Immunosuppressive Neutrophil Population in Human Gastric Cancer That Promotes Disease ProgressionZhiguo Shan, Yongliang Zhao, Jinyu Zhang, Zongbao Yan, Tingting Wang, Fangyuan Mao, Yongsheng Teng, Liusheng Peng, Wanyan Chen, Pan Wang , Ping Cheng, Wenqing Tian, Jun Chen, Weisan Chen, Yuan Zhuang*Advanced ScienceDOI: 10.
1002/advs.
202103543Click "Read the original text" in the lower left corner to view the original text of the paper
.
Introduction to AdvancedScience Journal Advanced Science is a high-quality open-source journal founded by Wiley in 2014.
It publishes innovative achievements and cutting-edge progress in various fields such as materials science, physical chemistry, biomedicine, and engineering
.
The journal is committed to maximizing the dissemination of scientific research to the public, and all articles are freely available
.
The latest impact factor is 16.
806, and the 2020 SCI journals of the Chinese Academy of Sciences are divided into the Q1 area of materials science and the Q1 area of engineering technology
.
Press and hold the QR code on the official WeChat platform of AdvancedScienceNewsWiley's scientific research information to follow us and share cutting-edge information｜Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com
