Remodeling the Tumor Immune Environment in Breast Cancer via Bortezomib-based Combination Therapy.

While proteasome inhibitors have revolutionized the treatment of hematologic malignancies and significantly improved patient survival, their efficacy in solid tumors remains limited. The recent work by Tang and colleagues demonstrates a novel combination strategy to overcome this limitation. Their study reveals that bortezomib, combined with either tetrathiomolybdate or AMD3100, synergistically kills breast cancer by downregulating expression of the proteasome subunit PSMB5. Crucially, the in vivo antitumor efficacy of these combinations is strictly dependent on an intact immune system, enabling cytotoxic CD8⁺ T cell responses. Although this study raises important mechanistic questions for future investigation, it significantly opens new avenues for expanding the therapeutic application of proteasome inhibitors in solid tumors.