Bacterial tumor therapy is commonly thought to be based on the induction of an inflammatory response at the site of the tumor as a result of the accumulation of extracellular bacteria at this immunologically privileged site. In our experiments, the profound reduction of TAMs was associated with complete tumor regression. The simplest interpretation of these data would be that TAMs are required to support tumor growth. However as we observed a massive infiltration of inflammatory cells simultaneous with bacterial infection and TAM depletion inflammation might also contribute to tumor regression. The extracellular BS176DaroA mutant did not induce caspase-1 processing and thus did neither induce IL-1b and IL-18 activation nor deplete TAMs. Therefore it is likely that for the induction of the inflammatory response by M90TDaroA targeting of macrophages is also a necessary factor. However the low dose bacteria found under these conditions makes it difficult to come up with a firm conclusion in this respect. As neutrophils have been described to be potential mediators of inflammation induced tumor Metamizole sodium hydrate regression it may be interesting in the future to determine whether M90TDaroA can induce neutrophil infiltration in the presence or absence of TAMs. Targeting TAMs as a strategy for bacterial tumor therapy may have the advantage that a stable cell population is attacked as opposed to the phenotypically unstable tumor cell population, that may quickly give rise to resistant cells. On the other hand macrophages found in tumors may potentially stimulate or inhibit tumor growth. It will therefore be important in the future to develop markers that differentiate between TAM populations and allow identification of tumors where TAM removal may be beneficial. Although at first sight Shigella would seem to be an unlikely candidate as a therapeutic agent based on its pathogenicity, the fact that attenuation was readily Riboflavin achieved and that a small number of bacteria at the tumor site was sufficient to induce a dramatic anti-tumor effect suggests that further investigation is warranted.