Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 39510069.
- Also identified by DOI 10.1016/j.xcrm.2024.101799 and PMC identifier 11604542.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Only a subset of patients with breast cancer responds to immune checkpoint blockade (ICB). To better understand the underlying mechanisms, we analyze pretreatment biopsies from patients in the I-SPY 2 trial who receive neoadjuvant ICB using multiple platforms to profile the tumor microenvironment. A variety of immune cell populations and markers of immune/cytokine signaling associate with pathologic complete response (pCR). Interestingly, these differ by breast cancer receptor subtype. Measures of the spatial distributions of immune cells within the tumor microenvironment, in particular colocalization or close spatial proximity of PD-1<sup>+</sup> T cells with PD-L1<sup>+</sup> cells (immune and tumor cells), are significantly associated with response in the overall cohort as well as the in the triple negative (TN) and HR<sup>+</sup>HER2<sup>-</sup> subtypes. Our findings indicate that biomarkers associated with immune cell signaling, immune cell densities, and spatial metrics are predictive of neoadjuvant ICB efficacy in breast cancer.
Medical subject headings
- Neoadjuvant Therapy
- Breast Neoplasms
- Immune Checkpoint Inhibitors
- Biomarkers, Tumor
- Tumor Microenvironment