Abstract B63: The utility and mechanistic basis of CTLA-4 and PD-1 immunotherapeutic checkpoint inhibitors in enhancing tumor-specific adaptive responses to effectively treat triple-negative breast cancer

While most breast cancers driven by estrogen-mediated signaling (ER+) or HER2 expression (HER2+) can be effectively treated by agents targeting these pathways, recent deep sequencing efforts have failed to identify widespread targetable drivers in Triple Negative Breast Cancers (TNBCs). Despite a lack of unifying drivers, our lab and others have uncovered that these cancers are highly inflammatory and associated with higher numbers of infiltrating immune cells (including CD8+ T-cells and Foxp3+ T-regulatory cells) , as well as expressing immuno-suppressive molecules (such as PD-L1). We hypothesized that despite TNBC molecular heterogeneity, the intrinsic inflammatory and immuno-suppressive features of these cancers could make them highly susceptible to checkpoint inhibitor-based immunotherapy. To test this hypothesis, we explored the utility and mechanistic basis of both PD-1 and CTLA-4 inhibition in generating tumor-specific immunity in an established murine model of TNBC.To test this hypothesis, we utilized a murine TNBC line (E0771) engineered with an OVA antigen to track and quantify tumor-specific immune responses. Consistent with patient samples, we found that TNBC tumors from this model contained significant numbers of T-cell infiltrates, a large proportion of which were CTLA-4+ PD-1+ Foxp3 T-regulatory cells (~66% of CD4+ TILs). We further found that TNBC tumor cells expressed surface PD-L1, which was significantly enhanced by INF-gamma stimulation. While these tumor-...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Microenvironment and Immunotherapy: Poster Presentations - Proffered Abstracts Source Type: research