Neoadjuvant Pembrolizumab With Chemotherapy Effective for Patients With Triple-negative Breast Cancer

Adding pembrolizumab to conventional neoadjuvant cytotoxic chemotherapy (NAC) may improve survival outcomes in triple-negative breast cancer, according to a study presented at the 2024 San Antonio Breast Cancer Symposium.

Researchers evaluated 20 cases for residual TNBC following NAC using Visium Spatial Gene Expression. Data was assessed with Spacer Ranger, aligned to GRCh38, and analyzed using the Seurat R package, the researchers noted. Expression data was normalized and batched with SCTransform and RunHarmony. Cell types and Hallmark pathway scores were discerned using AddModuleScore, and differential gene expression was performed using FindMarker in Seurat and ClusterProfiler.

In DEG analysis, the study showed that CXCL9, CXCL10 and CXCL13 increased in PEM+NAC whereas CCL18 and CD36 in NAC group (FDR <0.01, respectively). Moreover, the study found that in tumor associated Macs, CXCL9 and CXCL10 expressed Mac were nearer by cancer cells in PEM+NAC group than NAC group even though SPP1 Mac also closer to cancer cells in PEM+NAC group compared to NAC group (Ps <0.05). Furthermore, the researchers noted that CD69 and PDCD1 expressed exhausted CD8+ T cells were farther from cancer cell in PEM+NAC group compared to distance in NAC group.

“After PEM+NAC, residual TNBC more closely interacted CXCL9+/CXCL10+ macrophages even though SPP1+ macrophages with hypoxia also be near to tumor cells compared to those in NAC only. In addition, PEM+NAC expelled exhausted CD8 T cells from cancer in this spatial transcriptomic analysis. Based on these finding, we suggested that adding pembrolizumab to NAC would modulate tumor infiltrating immune cells, which may contribute better survival outcomes,” the researchers concluded.

Reference

Kim J, Park K, Shin J, et al. Spatial transcriptomic analysis for tumor infiltrating immune microenvironment modulation by neoadjuvant pembrolizumab with chemotherapy for patients with triple negative breast cancer. Abstract #SESS-1044. Presented at the 2024 San Antonio Breast Cancer Symposium; December 10-13, San Antonio, Texas.