By L‐R interaction analysis, these M2‐type macrophages may regulate T cell activities through multiple signalling pathways, including CD86‐CTLA4, SPP1‐CD44, CLEC2B‐KLRB1 and LGALS9‐CD44, which may provide novel immune therapy targets for osteosarcoma. This evidence concerns the gene SPP1 and osteosarcoma.