Le traitement anti-mCTLA-4 entraîne des effets de réponse immunitaire précoce et tardive dans un modèle murin de carcinome colorectal


David Draper, Alden Wong, Stacey Roys, Scott Wise, and Maryland Rosenfeld Franklin



Réunion annuelle de l'AACR

POSTER | Anti-mCTLA-4 Treatment Results in Early and Late Immune Response Effects in Murine Model of Colorectal Carcinoma (PDF)


Introduction and Background:

  • During pre-clinical research, analysis of the tumor immune response at a single post-treatment timepoint is often standard when therapeutic mechanism of action is investigated.
  • The use of a single sampling point for analysis can limit research on new immune modulation therapies as it provides only a partial view into the dynamic nature of the developing immune response in the tumor.
  • In this study we examined the kinetics of tumor-directed immune infiltration and activation on day 11 and day 17 post-implantation using the CT26 model for colorectal carcinoma.
  • The CT26 model is moderately responsive to checkpoint inhibition. To examine early and late effects that checkpoint inhibition has on the immune response, tumor-bearing mice were treated with anti-mCTLA-4. Tumor analysis corresponded to day 4 and day 10 post-treatment.
  • Endpoints analyzed consisted of:
    • 11 distinct tumor-infiltrating subsets
    • CD8+ T cell activation marker expression
    • T cell cytokine analysis
    • Effector/Memory T cell phenotype
  • We hypothesized that multiple sampling points would uncover unique immune subset specific profiles of infiltration and activation in the CT26 tumor.