Previous studies have shown the potential role of SPP1 + macrophages on effector T cells, hypothetically separate from the M1/M2 dogma16; however, there is limited understanding of whether SPP1 + macrophages can induce tumor-reactive CD8 + T cell exhaustion and dysfunction without an enriched M2 macrophage population16,36,37,54,55. This evidence concerns the gene SPP1 and neoplasm.