Anti-mCTLA-4 treatment results in early and late immune response effects in a murine model of colorectal carcinoma

AACR Annual Meeting

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.