Department of Clinical Sciences, Animal Cancer Center, Colorado State University, Ft. Collins, 80523, USA.
Cancer Immunol Immunother. 2010 Mar;59(3):367-78. doi: 10.1007/s00262-009-0755-y. Epub 2009 Aug 23.
Clinical studies over the past several years have reported that metastasis-free survival times in humans and dogs with osteosarcoma are significantly increased in patients that develop chronic bacterial osteomyelitis at their surgical site. However, the immunological mechanism by which osteomyelitis may suppress tumor growth has not been investigated. Therefore, we used a mouse model of osteomyelitis to assess the effects of bone infection on innate immunity and tumor growth. A chronic Staphylococcal osteomyelitis model was established in C3H mice and the effects of infection on tumor growth of syngeneic DLM8 osteosarcoma were assessed. The effects of infection on tumor angiogenesis and innate immunity, including NK cell and monocyte responses, were assessed. We found that osteomyelitis significantly inhibited the growth of tumors in mice, and that the effect was independent of the infecting bacterial type, tumor type, or mouse strain. Depletion of NK cells or monocytes reversed the antitumor activity elicited by infection. Moreover, infected mice had a significant increase in circulating monocytes and numbers of tumor associated macrophages. Infection suppressed tumor angiogenesis but did not affect the numbers of circulating endothelial cells. Therefore, we concluded that chronic localized bacterial infection could elicit significant systemic antitumor activity dependent on NK cells and macrophages.
近年来的临床研究报告称，患有骨肉瘤的人类和犬类患者，如果在手术部位发生慢性细菌性骨髓炎，其无转移存活时间会显著延长。然而，尚未研究骨髓炎可能抑制肿瘤生长的免疫机制。因此，我们使用骨髓炎的小鼠模型来评估骨感染对固有免疫和肿瘤生长的影响。在 C3H 小鼠中建立了慢性葡萄球菌骨髓炎模型，并评估了感染对同种异体 DLM8 骨肉瘤生长的影响。评估了感染对肿瘤血管生成和固有免疫（包括 NK 细胞和单核细胞反应）的影响。我们发现骨髓炎可显著抑制小鼠肿瘤的生长，并且这种作用与感染的细菌类型、肿瘤类型或小鼠品系无关。NK 细胞或单核细胞耗竭可逆转感染引起的抗肿瘤活性。此外，感染小鼠的循环单核细胞和肿瘤相关巨噬细胞数量明显增加。感染抑制肿瘤血管生成，但不影响循环内皮细胞的数量。因此，我们得出结论，慢性局部细菌性感染可引发依赖 NK 细胞和巨噬细胞的显著全身性抗肿瘤活性。
