Vaccination Causes a Clear Subtype Shift of Tumor Infiltrating Treg in MuPrime™ Mouse Breast Cancer Homografts
Annie Xiaoyu An, Davy Xuesong Ouyang, Jinping Li, Li Chen, and Henry Q.X. Li
Tumor infiltrating lymphocytes, including regulatory T cells (Treg), are believed to play a significant, but somewhat conflicting, role in cancer prognosis and sensitivity to immunotherapies, including immune checkpoint inhibitors (ICI).
FoxP3+ is considered to be a key marker of Treg. Recent research has indicated significant heterogeneity of Treg with different levels of FoxP3 and associated functional variations. This Treg heterogeneity may explain some of the conflicting observations in I/O response, and it would be interesting to investigate how this heterogeneity influences ICI treatment.
We have previously developed a breast cancer homograft model with poor response to anti-PD-1/PD-L1 inhibitors. In this model, prior vaccination seems to potentially render the tumor sensitive to PD-1/PD-L1 inhibition, with increased CD8+ TIL observed in the treated tumors. This poster explores the underlying mechanism of this vaccination, through extensive immunophenotyping of TILs in the vaccinated tumors.
Read this Poster to Discover:
- That vaccination is shown to reduce FoxP3 positive cells in non-treated animals
- That prior vaccination induces a dramatic shift of TIL-Treg from a FoxP3lo (naïve Treg) to FoxP3hi (effector Treg) population
- That the TIL-eTreg status, as opposed to naïve Treg, could play a critical role in tumor response to checkpoint inhibitor treatment, and that methods to change TIL-eTreg (such as vaccination) could be an important strategy to enhance checkpoint inhibitor treatment