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Containment of Tumor-Colonizing Bacteria by Host Neutrophils

Molecular Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany

Requests for reprints: Kathrin Westphal, Helmholtz Center for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany. Phone: 49-531-6181-5109; Fax: 49-531-6181-5002; E-mail: kathrin.westphal{at}helmholtz-hzi.de.

Key Words: tumor-targeting • bacteria • neutrophils • bacterial distribution • neutrophil depletion

Administration of facultative anaerobic bacteria like Salmonella typhimurium, Shigella flexneri, and Escherichia coli to tumor-bearing mice leads to a preferential accumulation and proliferation of the microorganisms within the solid tumor. Until now, all known tumor-targeting bacteria have shown poor dissemination inside the tumors. They accumulate almost exclusively in large necrotic areas and spare a rim of viable tumor cells. Interestingly, the bacteria-containing necrotic region is separated from viable tumor cells by a barrier of host neutrophils that have immigrated into the tumor. We here report that depletion of host neutrophils results in a noticeably higher total number of bacteria in the tumor and that bacteria were now also able to migrate into vital tumor tissue. Most remarkably, an increase in the size of the necrosis was observed, and complete eradication of established tumors could be observed under these conditions. Thus, bacteria-mediated tumor therapy can be amplified by depletion of host neutrophils. [Cancer Res 2008;68(8):2952–60]