The interplay between cytokines and immune checkpoints in breast cancer therapy

Breast cancer (BC) immunotherapy has transformed treatment paradigms, yet response rates remain limited by the complex interplay between cytokine networks and immune checkpoints. This review synthesizes emerging evidence on how cytokines dynamically regulate immune checkpoint expression and function within the breast tumor microenvironment. We examine pro-tumorigenic cytokine circuits alongside immunostimulatory pathways. A key focus is the subtype-specific nature of these interactions, with triple-negative breast cancers (TNBC) exhibiting distinct cytokine-checkpoint crosstalk compared to hormone receptor-positive subtypes. The review highlights innovative therapeutic strategies, including cytokine-targeting agents in clinical trials and engineered approaches like spatial-targeted nanocarriers. We further discuss how cutting-edge technologies from single-cell RNA sequencing to spatial proteomics are revealing novel biomarker opportunities. By decoding these intricate immune dialogues, this review provides a framework for developing precision immunotherapy combinations tailored to BC immunological heterogeneity.