: IL-1 family members have multiple pleiotropic functions affecting various tissues and
cells, including the regulation of the immune response, hematopoietic homeostasis, bone
remodeling, neuronal physiology, and synaptic plasticity. Many of these activities are involved in
various pathological processes and immunological disorders, including tumor initiation and
progression. Indeed, IL-1 family members have been described to contribute to shaping the tumor
microenvironment (TME), determining immune evasion and drug resistance, and to sustain tumor
aggressiveness and metastasis. This review addresses the role of IL-1 family members in bone
sarcomas, particularly the highly metastatic osteosarcoma (OS) and Ewing sarcoma (EWS), and
discusses the IL-1-family-related mechanisms that play a role in bone metastasis development. We
also consider the therapeutic implications of targeting IL-1 family members, which have been
proposed as (i) relevant targets for anti-tumor and anti-metastatic drugs; (ii) immune checkpoints
for immune suppression; and (iii) potential antigens for immunotherapy
