Background::Previous evidence suggests inflammation may be a double-edged sword with cancer-promoting and cancer suppressing function. In this study, we explore the impact of local and systemic inflammation on cancer growth.Methods::Female BALB/C mice were subcutaneously implanted with foreign body (plastic plates) to build up a local inflammation and intraperitoneally injected with PolyIC or lipopolysaccharides (LPS) to build up a systemic inflammation, followed by subcutaneous injection of 5 × 10 5 colon cancer cells. Immunohistochemistry and enzyme linked immunosorbent assay were utilized to detect the Ki67 and interleukin (IL) 6, IL-1β, and monocyte chemoattractant protein-1 expression in the tumor tissues and serum, respectively. The distributions of immune cells and expression of toll-like receptors (TLRs) were evaluated by flow cytometry (FCM) and quantitative real time-polymerase chain reaction. Results::The results showed that local inflammation induced by foreign body implantation suppressed tumor growth with decreased tumor weight ( P = 0.001), volume ( P = 0.004) and Ki67 index ( P < 0.001). Compared with the control group, myeloid-derived suppressive cells sharply decreased ( P = 0.040), while CD4 + T cells slightly increased in the tumor tissues of the group of foreign body-induced local inflammation ( P = 0.035). Moreover, the number of M1 macrophages ( P = 0.040) and expression of TLRs, especially TLR3 ( P < 0.001) and TLR4 ( P < 0.001), were significantly up-regulated in the foreign body group. Contrarily, tumor growth was significantly promoted in LPS or PolyIC-induced systemic inflammation ( P = 0.009 and 0.006). FCM results showed M1 type macrophages ( P = 0.017 and 0.006) and CD8 + T cells ( P = 0.031 and 0.023) were decreased, while M2 type macrophages ( P = 0.002 and 0.007) were significantly increased in tumor microenvironment of LPS or PolyIC-induced systemic inflammation group. In addition, the decreased expression of TLRs was detected in LPS or PolyIC group. Conclusions::The foreign body-induced local inflammation inhibited tumor growth, while LPS or PolyIC-induced systemic inflammation promoted tumor growth. The results suggested that the different outcomes of tumor growth might be attributed to the infiltration of anti-tumor or pro-tumor immune cells, especially M1 or M2 type macrophages into tumor microenvironment.

Inflammation;Cancer;Macrophage;Toll-like receptor

Liu Xinghan;Jiang Qi;Shen Sunan;Hou Yayi

The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China;Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China

中华医学杂志（英文版）

[1]Liu Xinghan;Jiang Qi;Shen Sunan;Hou Yayi-.Local and systemic inflammation triggers different outcomes of tumor growth related to infiltration of anti-tumor or pro-tumor macrophages)[J].中华医学杂志（英文版）,2022(15):1821-1828

PolyIC

Local,systemic,inflammation,triggers,different,outcomes,tumor,growth,related,infiltration,macrophages,Background,Previous,evidence,suggests,may,double,edged,sword,cancer,promoting,suppressing,function,this,study,explore,impact,local,Methods,Female,BALB,mice,were,subcutaneously,implanted,foreign,body,plastic,plates,build,intraperitoneally,injected,lipopolysaccharides,LPS,followed,by,injection,10 ,colon,cells,Immunohistochemistry,enzyme,linked,immunosorbent,assay,utilized,Ki67,interleukin,monocyte,chemoattractant,protein,expression,tissues,serum,respectively,distributions,immune,toll,like,receptors,TLRs,evaluated,flow,cytometry,FCM,quantitative,real,polymerase,chain,reaction,Results,results,showed,that,induced,implantation,suppressed,decreased,weight,volume,Compared,control,group,myeloid,derived,suppressive,sharply,while,CD4 ,slightly,increased,Moreover,number,M1,especially,TLR3,TLR4,significantly,regulated,Contrarily,was,promoted,type,CD8 ,M2,microenvironment,addition,detected,Conclusions,inhibited,suggested,might,attributed,into,Inflammation,Cancer,Macrophage,Toll

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