(618e) High-Dimensional Analysis of the Tumor Immune Microenvironment of Metaplastic Breast Carcinoma

Metaplastic breast carcinoma (MBC) is an aggressive variant of triple-negative breast cancer that has poorer prognosis and increased propensity for metastasis, compared to other triple-negative breast cancers. Common treatments for other breast cancers -- chemotherapy, radiation therapy, and hormonal therapy -- have been ineffective. Furthermore, MBC is rare, accounting for approximately 1% of breast carcinomas, and has limited molecular research. Thus, a deeper understanding of the tumor immune microenvironment (TIME) to identify potential therapeutic targets is needed.

We leveraged imaging mass cytometry to investigate the TIME of three clinical subtypes of MBC. From the fixed tissue sections of 26 patients, we detected 35 markers on more than 160,000 cells, and identified 13 major tumor and immune cell types. Immune cells are differentially enriched in different MBC subtypes, representing potential targets for immunotherapy. Further spatial analysis revealed interesting immune–immune and immune–tumor interactions that can affect immunotherapy efficacy. This highly multiplexed analysis provides a framework that can readily be applied to investigate the TIME of other solid tumors for therapeutic target discovery.