Multiplexed imaging analysis of the tumor-immune microenvironment reveals predictors of outcome in triple-negative breast cancer

Triple-negative breast cancer, the poorest-prognosis breast cancer subtype, lacks clinically approved biomarkers for patient risk stratification and treatment management. Prior literature has shown that interrogation of the tumor-immune microenvironment may be a promising approach to fill these gaps. Recently developed high-dimensional tissue imaging technology, such as multiplexed ion beam imaging, provide spatial context to protein expression in the microenvironment, allowing in-depth characterization of cellular processes. We demonstrate that profiling the functional proteins involved in cell-to-cell interactions in the microenvironment can predict recurrence and overall survival. We highlight the immunological relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying interactions involving them to recurrence and survival. Multivariate analysis reveals that our methods provide additional prognostic information compared to clinical variables. In this work, we present a computational pipeline for the examination of the tumor-immune microenvironment using multiplexed ion beam imaging that produces interpretable results, and is generalizable to other cancer types. Patwa, Yamashita et al. utilize multiplexed imaging to demonstrate that profiling cell-to-cell interactions in the microenvironment can reveal predictors of recurrence and overall survival in triple-negative breast cancer, especially highlighting the relevance of immunoregulatory proteins. The authors also use multivariate analysis to provide additional prognostic information compared to clinical variables.

Automated summary

The study utilizes high-dimensional tissue imaging technology to analyze the tumor-immune microenvironment in triple-negative breast cancer patients, revealing that profiling cell-to-cell interactions in the microenvironment can predict recurrence and overall survival, especially highlighting the importance of immunoregulatory proteins.