This study investigates the role of CD24 in cancer immunotherapy, particularly in ovarian and triple-negative breast cancers. CD24, a glycosylated GPI-anchored surface protein, interacts with the inhibitory receptor Siglec-10 on tumor-associated macrophages (TAMs) to promote immune evasion. The authors found that many tumors overexpress CD24, and TAMs express high levels of Siglec-10. Genetic ablation of CD24 or Siglec-10, and monoclonal antibody blockade of the CD24-Siglec-10 interaction, robustly augmented phagocytosis of CD24-expressing human tumors. In vivo experiments showed that CD24 blockade reduced tumor growth and improved survival. These findings highlight CD24 as a promising target for cancer immunotherapy, particularly in ovarian and breast cancers, where responses to existing therapies are often limited.This study investigates the role of CD24 in cancer immunotherapy, particularly in ovarian and triple-negative breast cancers. CD24, a glycosylated GPI-anchored surface protein, interacts with the inhibitory receptor Siglec-10 on tumor-associated macrophages (TAMs) to promote immune evasion. The authors found that many tumors overexpress CD24, and TAMs express high levels of Siglec-10. Genetic ablation of CD24 or Siglec-10, and monoclonal antibody blockade of the CD24-Siglec-10 interaction, robustly augmented phagocytosis of CD24-expressing human tumors. In vivo experiments showed that CD24 blockade reduced tumor growth and improved survival. These findings highlight CD24 as a promising target for cancer immunotherapy, particularly in ovarian and breast cancers, where responses to existing therapies are often limited.