Anxa2 drives the function of immune suppressive neutrophils in lung cancer

Anxa2 驱动肺癌中免疫抑制性中性粒细胞的功能

• 批准号: 10310981
• 负责人: A McGarry Houghton
• 金额: $ 4.02万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10310981
• 关键词: ANXA2 gene; Accounting; Address; Annexins; CD8-Positive T-Lymphocytes; Cancer Etiology; Cancer Patient; Cell Lineage; Cessation of life; Clinical; Clinical Trials; Data; Human; Immune; Immune checkpoint inhibitor; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Myelogenous; Non-Small-Cell Lung Carcinoma; PD-1/PD-L1; Phenotype; Play; Research Personnel; Role; Scientist; Specimen; Testing; Training; Tumor-Derived; anti-PD-1; anti-PD-L1 therapy; base; cancer type; career; cell type; checkpoint therapy; cohort; graduate student; immune checkpoint blockade; immune function; improved; neutrophil; novel therapeutics; skills; success

ABSTRACT Although immune checkpoint inhibitor (ICI) therapy has been a tremendous clinical success, just ~20% of non- small cell lung cancer (NSCLC) patients respond to anti-PD1/PDL1 therapy. In efforts to improve upon this figure, the field has launched over 800 clinical trials (across all cancer types) testing novel therapeutics in conjunction with immune checkpoint blockade. Unfortunately, such trials have been based largely on theoretical considerations and not by data obtained from actual human cancer specimens. Notably, very few of these trials address myeloid lineage cells and none of them address the neutrophil lineage. Our group recently undertook a comprehensive immune phenotyping project to identify potential immune suppressive factors in human NSCLC. We found that neutrophils were the most prevalent immune cell type out of the 51 immune cell types and subtypes assessed. More importantly, the presence of neutrophil lineage cells inversely correlated with CD8+ lymphocyte content within the TME. Here, we will show tumor-derived Annexin-A2 polarizes neutrophils to an immune suppressive phenotype and determine the mechanisms by which it does so. More importantly, this project will provide the necessary training ground for the graduate student to obtain the skills and critical examination of data to progress in his career towards an independent scientist.

摘要