A tumor-promoting inflammatory SPP1+ macrophage-IL-6-CRP axis drives immune dysfunction in bladder cancer - PubMed
3 hours ago
- #immunotherapy
- #macrophages
- #bladder cancer
- Immune checkpoint blockade (ICB) has transformed urothelial bladder cancer (UC) treatment, but response rates are still limited.
- Inflammation drives disease progression and treatment resistance, with macrophages influencing the tumor microenvironment (TME).
- High blood C-reactive protein (CRP) correlates with poor UC outcomes, but its link to the TME was unclear.
- Elevated plasma IL-6 and CRP are associated with increased tumor macrophage infiltration in ICB-treated patients.
- Single-cell RNA sequencing reveals immunosuppressive SPP1+ macrophages are enriched in TMEs of patients with high plasma IL-6.
- SPP1+ macrophages suppress T cell activity via IL-6 signaling, while CXCL9+ macrophages enhance T cell activation.
- The study connects systemic inflammation to local immune dysfunction and identifies a macrophage-driven axis linked to ICB resistance.