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S100A8 and S100A9 are members of the S100 protein family comprising a multigenic group of non-ubiquitous cytoplasmic Ca2+-binding proteins of the EF-hand type.They are abundant in cells of the myeloid lineage and are secreted from phagocytes upon cellular activation.Extracellular S 100Ag/A9 displays apoptosis-inducing activity toward various tumor cell lines via a Receptor of Advanced Glycation End product (RAGE)-independent pathway.Together with the demonstration that S 100A8 and S 100A9 positive cells, macrophages and polymorphonuclear Ieukocytes, accumulate along the invasive margin of carcinoma S 100A8/A9 has been proposed being a powerful apoptotic agent that plays an important role in the antitumor response of the innate immune system.Since it spears the risk to induce auto-immune response, S 100A8/A9 may serve as lead compound for cancer-selective therapeutics.