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肿瘤微环境中的炎症与免疫

Inflammation and immunity in the tumor environment.

机构信息

Department of Gastroenterology, University Clinic Rostock, Rostock, Germany.

出版信息

Dig Dis. 2010;28(4-5):574-8. doi: 10.1159/000321062. Epub 2010 Nov 18.

DOI:10.1159/000321062
PMID:21088404
Abstract

The relationship between inflammation, innate immunity and cancer is widely accepted. Cancer-associated inflammation includes infiltrating leukocytes, cytokines, chemokines, growth factors, lipid messengers and matrix-degrading enzymes. Tumor-associated macrophages and lymphocyte subpopulations are major components of the leukocyte infiltrate in most tumors. However, the cytokine and chemokine expression profile of the tumor microenvironment may be more relevant than its specific immune cell content. Apart from inflammatory cells, tumor stroma consists of new blood vessels and connective tissue. Many factors produced by tumor cells promote tumor angiogenesis and generation of extracellular matrix. Investigations regarding the link between inflammation and cancer are vital for identifying cell or protein targets for cancer prevention and therapy. Based on the relation between inflammation and cancer, different forms of immunotherapy have been developed. In a mouse model, we investigated the potential of Streptococcus pyogenes to achieve a bacteria-related immune response against tumor cells followed by tumor regression. As a model of pancreatic carcinoma, the aggressively growing and poorly immunogenic Panc02 tumor model was chosen. Our findings showed that a local application of bacteria mediates complete tumor regression. Future investigations should focus on the optimization of immunotherapeutic approaches that incorporate live bacteria or bacterial components.

摘要

炎症、先天免疫和癌症之间的关系已被广泛接受。癌症相关的炎症包括浸润的白细胞、细胞因子、趋化因子、生长因子、脂质信使和基质降解酶。肿瘤相关的巨噬细胞和淋巴细胞亚群是大多数肿瘤中白细胞浸润的主要成分。然而,肿瘤微环境中的细胞因子和趋化因子表达谱可能比其特定的免疫细胞含量更为相关。除了炎症细胞外,肿瘤基质还包括新的血管和结缔组织。肿瘤细胞产生的许多因素促进了肿瘤血管生成和细胞外基质的产生。研究炎症与癌症之间的联系对于确定癌症预防和治疗的细胞或蛋白靶点至关重要。基于炎症和癌症之间的关系,已经开发出了不同形式的免疫疗法。在小鼠模型中,我们研究了化脓性链球菌(Streptococcus pyogenes)实现针对肿瘤细胞的细菌相关免疫反应并随后导致肿瘤消退的潜力。选择侵袭性生长和免疫原性差的 Panc02 胰腺癌细胞作为胰腺癌模型。我们的研究结果表明,局部应用细菌可介导完全的肿瘤消退。未来的研究应侧重于优化免疫治疗方法,将活菌或细菌成分纳入其中。

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