title: Methods to Evaluate the Antitumor Activity of Immune Checkpoint Inhibitors in Preclinical Studies.
abstract: Immune checkpoint inhibitors (ICI) are a new class of drugs characterized by their ability to enhance antitumor immune responses through the blockade of critical cell surface receptors involved in the maintenance of peripheral tolerance. The recent approval of ICI targeting CTLA-4 or PD-1 for the treatment of cancer constitutes a major breakthrough in the field of oncology and demonstrates the potential of immune-mediated therapies in achieving durable cancer remissions. The identification of new immune regulatory pathways that could be targeted to reactivate or boost antitumor immunity is now a very active field of research. In this context, the use of syngeneic mouse models and immune monitoring techniques are the cornerstone of proof-of-concept studies. In this chapter, we describe the general methodology to evaluate antitumor activity of ICI in immunocompetent mice. We outline protocols to reliably establish tumors in mice and generate lung metastasis through tail vein injections with the aim of testing the efficacy of ICI. We also present methods to analyze the composition of the tumor immune-infiltrate by multicolor flow cytometry.
authors: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, 900 Rue Saint-Denis, 10ième étage, Montréal, QC, Canada, H2X0A9.|Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, 2940 chemin de Polytechnique, Montréal, QC, Canada.
authors: Bertrand
authors: B
authors: Allard
authors: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, 900 Rue Saint-Denis, 10ième étage, Montréal, QC, Canada, H2X0A9.|Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, 2940 chemin de Polytechnique, Montréal, QC, Canada.
authors: David
authors: D
authors: Allard
authors: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du Cancer de Montréal, 900 Rue Saint-Denis, 10ième étage, Montréal, QC, Canada, H2X0A9. john.stagg@umontreal.ca.|Faculté de Pharmacie, Université de Montréal, Pavillon Jean-Coutu, 2940 chemin de Polytechnique, Montréal, QC, Canada. john.stagg@umontreal.ca.
authors: John
authors: J
authors: Stagg
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology* / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D056747:Immunomodulation / Q000187:drug effects*; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors
chemical_list: D000074322:Antineoplastic Agents, Immunological; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Cancer; Immune-checkpoint; Immuno-oncology; PD-1; PD-L1