Delayed macrophage targeting by clodronate liposomes worsens the progression of cytokine storm syndrome.

Excessive macrophage activation and production of pro-inflammatory cytokines are hallmarks of the Cytokine Storm Syndrome (CSS), a lethal condition triggered by sepsis, autoimmune disorders, and cancer immunotherapies. While depletion of macrophages at disease onset protects from lethality in an infection-induced CSS murine model, patients are rarely diagnosed early, hence the need to characterize macrophage populations during CSS progression and assess the therapeutic implications of macrophage targeting after disease onset. In this study, we identified MHCIIF4/80Tim4 macrophages as the primary contributors to the pro-inflammatory environment in CSS, while CD206F4/80Tim4 macrophages, with an anti-inflammatory profile, become outnumbered.

Cancer-associated fibroblast-derived Dickkopf-1 suppresses NK cell cytotoxicity in breast cancer.

Breast cancer is poorly immunogenic, hence able to evade T cell recognition and respond poorly to immune checkpoint blockade. Breast cancer cells can also evade NK cell-mediated immune surveillance, but the mechanism remains enigmatic. Dickkopf-1 (DKK1) is a Wnt/b-catenin inhibitor, whose levels are increased in breast cancer patients and correlate with reduced overall survival.

Effective Treatment of Established Bone Metastases Can Be Achieved by Combinatorial Osteoclast Blockade and Depletion of Granulocytic Subsets.

Osteoclast (OC) blockade has been successful in reducing tumor growth in bone in preclinical settings, but antiresorptive drugs, such as zoledronic acid (ZA), fail to improve the overall survival rate of patients with bone metastasis despite ameliorating skeletal complications. To address this unmet clinical need, we interrogated what other cells modulated tumor growth in bone in addition to OCs. Because myeloid-derived suppressor cells (MDSC)-heterogeneous populations expressing CD11b, Ly6C, and Ly6G markers-originate in the bone marrow and promote tumor progression, we hypothesized that their accumulation hinders ZA antitumor effects.