| Colorectal cancer,including rectum cancer and colon cancer,is the third highest incidence of cancer worldwide,behind the lung cancer and breast cancer.In China,the incidence of colorectal cancer is lo?w,while the mortality rate is relatively high,when compared with Western countries.In recent years,the incidence of colorectal cancer has a clear upward trend,at the same time,the age of patients tends to younger.Colorectal cancer evolves from the intestinal epithelial benign polyps,and its causes with multiple factors,including genetic mutations,environmental stimulations,poor diet and genetic factors.Chemokines are a class of small molecule protein,interacting with the G protein-coupled receptors,triggering series of intracellular reactions,and thus exert their biological function.Tumor cells can secrete chemokines,but also can produce reactions,such as recruit endothelial cells,immune surveillance,adjust the surface proteins of tumor cell to evade immune surveillance,which in turn promote their own development and to increase the transfer to distance site.In many physiological and pathological processes,such as angiogenesis,inflammatory diseases,promote tumor and anti-tumor response,chemokines plays an important role.Currently,the treatment for colorectal cancer is still based on the traditional surgical,combining with radiotherapy and chemotherapy.With the progress of science and technology,as well as tumor-related disciplines,the understanding of tumor also unceasingly thoroughly,and the treatment strategies also enriched.Among the new treatment methods,biotherapy is the most representative undoubtedly,and the gene therapy and cell therapy have become the focus recently.In gene therapy,many scholars will combines immune genes,tumor suppressor genes with oncolytic virus by the genetic engineering methods,increasing safety and improving the treatment effect.Cell therapy,primarily adoptive immune cell therapy,has been widely used in clinical treatment.Adoptive immunotherapy,is to stimulate and activate cells with anti-tumor effects in vitro by IL-2,CD3 monoclonal antibody and IFN-y.After the expansion,CIK cells were injected into the patients,and then achieve the purpose of anti-tumor by stimulating the patient's own immune system.Currently,the research focuses on DCs,TILs,CTLs and CIK cells,and has achieved a good result.CIK cells,NK-like T cells,which combines the powerful anti-tumor activity of T cells and the advantage of non-MHC restricted.CIK has a strong proliferation ability and a broad spectrum anti-tumor ability,can clear the remaining tiny lesions,and CIK has been researched and applicated more extensive.Therefore,it has a important theoretical and practical significance to improve the directional migration of CIK to tumor cells and enhances their oncolytic effect.So far,reports about expression profile of chemokine receptor expressed on human CIK cells are rare.Therefore,CIK cells was used as a research model of tumor targeting T cells,by detecting the expression profile of chemokine receptor expressed on CIK cells and chemokine expression profiles expressed by tumor tissue,and changing their expression profile rational,to enhance the directional migration ability of CIK cells.This paper aims to enhance CIK cell migrate to tumor.Firstly,detect the expression profile of chemokines expressed from colorectal cancer tissues,adjacent tissues and colon cancer cell lines;Secondly,culture CIK cells with human peripheral blood in vitro,and then detect the chemokine receptors expression profile by flow cytometry;Finally,stimulate the chemokine receptors on CIK,and test the ability of CIK migrate to the tumor cells.Research result:1.Compared to the adjacent tissue,the expression of CXCL10,CXCL11 in tumor tissue was significantly higher,while the CCL21 and CXCL12 was lower.2.Compared to the 293T cells,the expression of CCL22,CXCL10 and CXCL11 in colon cancer cell lines was significantly higher,and consistent with the tissue test results.3.The chemokines expression profiles of tumor tissue has a certain correspondence with the chemokine receptors expression profile on CIK(CXCL11/CXCR3).4.The expression of CXCR3 and CXCR4 was significantly higher than CCR4,CCR5 and CCR7 on surface of CIK cultured from colon cancer patients' peripheral blood.5.Compared with the colon cancer patients' CIK,the healthy donors' CIK has a similar chemokine receptor expression profile,while the express level was significantly lower.6.In the process of CIK culture,add the recombinant chemokine can increases their receptor expression level,and enhance the directional migration ability. |
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