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PD-L1 inhibitors (myeloid-specific) represent a class of targeted immunotherapies designed to selectively block programmed cell death 1 ligand 1 (PD-L1) on myeloid lineage cells (such as macrophages and osteoclast precursors) rather than globally. In preclinical models, myeloid-specific PD-L1 inhibition or deletion (e.g., using LysM-Cre;PD-L1 flox/flox systems) has been shown to suppress osteoclastogenesis and protect against obesity-related bone loss, as well as diminish bone metastases of breast cancer and melanoma. Unlike global PD-1/PD-L1 blockade, which can sometimes lead to skeletal adverse effects or cardiotoxicity, myeloid-specific targeting aims to preserve bone microarchitecture and limit systemic inflammatory side effects, such as immune-checkpoint-inhibitor-associated myocarditis.
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