Anti-mCTLA-4 treatment results in early and late immune response effects in a murine model of colorectal carcinoma
David Draper, Alden Wong, Stacey Roys, Scott Wise, and Maryland Rosenfeld Franklin
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.