Targeting MK2-Driven Stromal Senescence Sensitizes Breast Cancer Bone Metastasis to Immunotherapy

MK2-dependent senescent cancer-associated fibroblasts in bone metastases predict reduced overall survival, and MK2 targeting suppresses metastasis while expanding CD4 T cells and MHC-II myeloid cells.

• Why it matters: Bone metastatic breast cancer is linked to an immunosuppressive senescence-associated secretory phenotype that limits effective anti-tumor immunity.
• What they did: The study identified senescent CAFs with an MK2-dependent SASP in patient bone metastases, then used senCAF ablation, MK2 elimination in senCAFs, or pharmacologic MK2 inhibition, assessing immune populations and OX40L expression.
• The result: Myeloid cells failed to express OX40L, and combining an MK2 inhibitor with an OX40 agonist overcame this defect, enabling antigen-specific eradication of bone metastases and durable immunological memory after rechallenge.