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Life sciences · Journal article
Frontiers in Oncology · October 20, 2026
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The JAK-STAT signaling pathway serves as a critical hub for cytokine signal transduction, and its aberrant activation plays a decisive role in shaping the immune microenvironment of breast cancer. This review systematically elucidates how this pathway contributes to the construction of an immunosuppressive microenvironment through upregulating PD-L1 expression, recruiting and activating myeloid-derived suppressor cells (MDSCs), promoting regulatory T cell (Treg) generation, while concomitantly suppressing the functions of CD8+ T cells and natural killer (NK) cells. Although targeted therapy against this pathway, particularly in combination with immune checkpoint inhibitors, has demonstrated promising potential, several challenges remain, including pathway compensation, low inhibitor selectivity, associated toxicities, and the lack of predictive biomarkers. Future directions should focus on the development of highly selective STAT inhibitors, exploration of immunophenotype-guided combination strategies, establishment of robust biomarker systems, and in-depth investigation of the dynamic interplay between this pathway and the immune microenvironment, thereby providing a theoretical foundation for combined immunotherapy in breast cancer.