Conditional Genetic Ablation Mouse Models as a Tool to Study Cancer Immunosurveillance In Vivo

Methods Mol Biol. 2019:1884:161-176. doi: 10.1007/978-1-4939-8885-3_11.

Abstract

Over the last decades, it has been established that the immune system is crucial for the impediment of cancer development by recognizing and destroying transformed cells. This process has been termed cancer immunosurveillance. Small animal models have significantly facilitated our understanding of it. Dissecting the contribution of any specific immune cell type participating in this process requires the ability to specifically target it while leaving the other immune components as well as the cancer model system unperturbed in vivo. Here, we provide a simple and rapid protocol for the generation of transgenic mice expressing Cre recombinase in a cell type-specific manner-in our example we chose cells expressing Ncr1, which encodes for the surface protein NKp46-and the use of those mice to ablate NKp46+ cells in order to study their role in a model of cancer immunosurveillance against experimental pulmonary metastases. This protocol can easily be adapted to target other cell types and other cancer models.

Keywords: B16 melanoma cells; Cancer; Conditional cell ablation; Conditional gene targeting; Cre recombinase; Immunosurveillance; In vivo bioluminescent imaging; Luciferase; NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / genetics*
  • Antigens, Ly / immunology
  • Antigens, Ly / metabolism
  • Cell Line, Tumor
  • Female
  • Genes, Reporter / genetics
  • Immunologic Surveillance*
  • Integrases / genetics*
  • Intravital Microscopy / instrumentation
  • Intravital Microscopy / methods
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Luciferases, Firefly / chemistry
  • Luciferases, Firefly / genetics
  • Luminescent Measurements / instrumentation
  • Luminescent Measurements / methods
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Natural Cytotoxicity Triggering Receptor 1 / genetics*
  • Natural Cytotoxicity Triggering Receptor 1 / immunology
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / immunology

Substances

  • Antigens, Ly
  • Natural Cytotoxicity Triggering Receptor 1
  • Ncr1 protein, mouse
  • Luciferases, Firefly
  • Cre recombinase
  • Integrases