The tumor immune environment in advanced breast cancer following treatment with pembrolizumab and nab-paclitaxel

Metastatic breast cancer poses significant clinical challenge, necessitating improved treatment options. Immune checkpoint blockade approval for PD-L1+ triple-negative breast cancer highlights potential for durable response. However, PD-L1 diagnostics can be discordant and responses in PD-L1 low/negative patients emphasize the need for deeper understanding of tumor microenvironment (TME). In a single center phase II trial, specimens were obtained from 70 breast cancer patients at baseline, treatment cycle 1 featuring monotherapy using nab-paclitaxel (ER+/HER2- BC, cTNBC) or pembrolizumab (iTNBC), followed by combination therapy in cycle 2. We used PhenoImagerHT and NanoString for spatial phenotyping and gene expression analysis of ER+ cohort. Preliminary multiplex imaging (qMIF) showed correlation in cell phenotype, activation state, and spatial location. NanoString revealed transcriptional differences between responders and non-responders at baseline. Moreover, a positive relationship (r=0.8) was found between CTLs and macrophage count, validating qMIF targets. Our research extends to study tumor immune infiltrates and gene expression in cTNBC (n= 30) and iTNBC (n= 20) cohorts. The final results will determine intrinsic subtype signatures of each cohort and study crosstalk between different cell types in the TME. In conclusion, our approach aims to enhance the understanding of treatment response and TME's role in metastatic breast cancer for improved therapeutic strategies.