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Cellular reprogramming during anti-PD-1 and chemotherapy treatment in early-stage primary hormone receptor-positive breast cancer.


ABSTRACT: The efficacy of immune checkpoint inhibitors combined with chemotherapy varies among breast cancer subtypes and is particularly less effective in hormone receptor-positive (HR + ) breast cancers. Here, we analyze pre-, on-, and post-treatment biopsies from 20 female patients with stage II-III HR+ breast cancer who participated in a clinical trial of neoadjuvant chemo-immunotherapy with nab-paclitaxel and pembrolizumab. Through single-nucleus RNA and ATAC sequencing of these tumor biopsies, we identified gene expression metaprograms (MPs) associated with differential therapy responses. Here we show that favorable responders exhibit increased activity in pathways related to tumor state transition, T cell effector functions, and pro-inflammatory macrophage states. Unfavorable responders demon

SUBMITTER: Fu J 

PROVIDER: S-EPMC12663104 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature