Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer

The accumulation of senescent cells in the tumor microenvironment can drive tumorigenesis in a paracrine manner through the senescence-associated secretory phenotype (SASP). Using a new p16-FDR mouse line, we show that macrophages and endothelial cells are the predominant senescent cell types in murine KRAS-driven lung tumors. Through single cell transcriptomics, we identify a population of tumor-associated macrophages that express a unique array of pro-tumorigenic SASP factors and surface proteins and are also present in normal aged lungs. Genetic or senolytic ablation of senescent cells, or macrophage depletion, result in a significant decrease in tumor burden and increased survival in KRAS-driven lung…

• OH
  Oregon Health and Science University
• KI
  Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
• CR
  Cancer Research UK

  Awards: A25117, C62187/A29760, C62187/A26989, C9685/A25117, C15075/A28647, BRC-1215-20014, RG86786, C54322/A27727
• NI
  National Institute for Health and Care Research

  Award: BRC-1215-20014
• DO
  Department of Health and Social Care
• UC
  University College London
• CW
  CHILDREN with CANCER UK

  Award: 15-190
• GO
  Great Ormond Street Hospital for Children
• NI
  National Institutes of Health
• MR
  Medical Research Council

  Awards: MR/R000530/1, MR/T030534/1, BRC-1215-20014, MC_U120085810, MR/T030534/1, MR/R000530/1
• NC
  NIHR Cambridge Biomedical Research Centre

  Award: BRC-1215-20014