| Traditional treatments for tumors include surgery,radiotherapy,and chemotherapy.Radical surgery has a good effect on most early tumors,but most of the early onset of the tumor is relatively insidious.The clinical findings are advanced,and the chance of radical surgery is lost,even if surgery Still have to face the problem of recurrence after the bundle.Chemotherapy and chemotherapy have certain curative effect on tumors,but because of the poor systemic basis of patients with advanced cancer,it is difficult to tolerate the side effects caused by high dose of radiotherapy and chemotherapy.Drug resistance and insensitivity to radiotherapy make traditional methods useless.With the rise of immunology and research on tumor immunotherapy,it is recognized that due to the negative regulation of tumor microenvironment and tumor cells,the immune system in the body is out of balance,and tumor cells are in an immunosuppressive and escape state,which is caused by tumors.The root cause of recurrence and metastasis.Therefore,enhancing the immune response of the body’s immune system to cancer has become a new breakthrough in combating gastric cancer.Since 2010,the FDA approved the first tumor vaccine in the history of humans to use the patient’s own dendritic cells to treat metastatic prostate cancer,sipuleucel-T [1],DC vaccine treatment has more prominent research results [2-4].At present,DC-CIK,a therapeutic tumor vaccine based on dendritic cells(DC),is a research hotspot in immunotherapy.DC-CIK cell therapy mainly refers to the cultivation of antigen-loaded dendritic cells(DC)in vitro [5].However,this treatment method is still in the clinical trial stage.Therefore,we must first analyze the safety and effectiveness of the data through clinical data.Under the premise of safety,we should look for the optimization strategy of DC to improve itseffectiveness.It is to develop a new generation of DC vaccine and improve its The key to clinical efficacy.Therefore,this study collected laboratory data and follow-up data from 72 clinical trials of advanced renal cell carcinoma DC-CIK cells,and evaluated clinical efficacy and prognosis through laboratory test indicators and return visit results.Through analysis,it is found that the safety of DC-CIK vaccine is acceptable,but the effectiveness needs to be improved.It is speculated that due to the inhibition of the immune system in vivo by the patient’s own tumor,the development of DC is not perfect and can not play a good role.TOLL-like receptor 8(Tolllikereceptors(TLR8)can be expressed in DCs and enhance DC antigen presentation by NFKB phosphorylation promoting cytokine TNF-α,IL-12 release and DC maturation [7].These cytokines can induce helper T cells.(T helper cell,Th)drifts in the direction of Th1,which is beneficial to inhibit the proliferation of regulatory T cells(Regulatory cells,Treg),thereby reversing immune tolerance and enhancing anti-tumor effect,but the regulation of TLR8 in DCs of gastric cancer patients is not known..In this study,we selected a novel highly selective TLR8 agonist VTX-2337 to stimulate DC in gastric cancer patients,to detect its regulation of immune function and the activation of T lymphocytes by DC after regulation,to verify whether VTX-2337 is in DC of gastric cancer patients.It can promote DC maturation and enhance its immune function and play an important role in the induction of T lymphocyte activation by DC as an adjuvant.According to Professor Wang Pin [6] in 2014,there is a Lnc RNA in DC that affects its differentiation and maturation and antigen recognition and presentation ability.It is named Lnc-DC,which is directly linked to STAT3 in cytoplasm.effect.However,whether the expression level of this Lnc RNA is normal in DCs of tumor patients is not known.Recent studies have shown that Lnc-DC regulates TLR9/STAT3 signaling in DCs and mediates the immune response of HBV.Therefore,maybe there a synergistic effectbetween Lnc-DC and TLR8 in gastric cancer patients.Therefore,this articlepurposes:1.Through the clinical trial data statistics,the clinical efficacy and prognosis analysis of DC-CIK in the treatment of advanced renal cell carcinoma,verify the safety of DC-CIK cell therapy;2.To explore the regulatory effect of TLR8 agonist VTX-2337 on DC culture in gastric cancer patients;3.Whether there is a difference in the expression level of Lnc-DC in normal human and gastric cancer patients DC and in agonist group and control group;method:1.Statistics of patients with advanced renal cell carcinoma who participated in DC-CIK clinical trials were analyzed with SPSS16.0,and the survival time of patients was reviewed and returned for prognosis analysis.2.Regulation of TLR8 agonist VTX-2337 on dendritic cells in gastric cancer patients and related signaling pathways(1)TLR8 agonists stimulate DCs in gastric cancer patients;(2)Western blot analysis of NF-κB and p NF-κB protein levels in DCs to confirm the role of TLR8 agonists;(3)Flow detection of DC surface mature marker molecules(HLA-DR,CD11 C,CD80,CD86,CD54,CD83);(4)ELISA detection of culture supernatant cytokines IL-12,TNF-α expression levels;(5)Co-culture of DC-T lymphocytes,flow detection of T cell surface activation markers(HLA-DRCD3,CD28).(6)qPCR was used to detect the content of lnc-DC in DCs of normal and gastric cancer patients as well as agonist group and control group;result:The first part of the research results:1.72 patients with renal cell carcinoma were treated with DC-CIK cells,and the data were incomplete and lost to follow-up in 30 cases.The remaining 42 cases had an objective response rate of 33.33%,the disease control rate was 73.81%,and the 1-year survival rate was 83%.The rate was 78% and the 3-year survival rate was maintained at 67.8%.The proportion of CD3+ CD8+ cells in peripheral blood was significantly increased(P=0.009),and the proportion of CD4+CD25+ cells,CD3+CD4+ cells and CD4+CD8+ was significantly decreased(P=0.026,P=0.028,P=0.04).3.Compared with pre-treatment,triglyceride levels were elevated(P=0.003).Pearson correlation analysis showed a positive correlation between serum triglyceride and B cell ratio in patients with advanced renal cell carcinoma(r=0.387,P=0.011).There was a positive correlation between cholesterol and NK cell ratio(r=0.362,P=0.018),and a high correlation between high-density cholesterol and regulatory T-cell ratio(r=-0.303,P=0.049).4 Univariate analysis showed that TNM staging,cell therapy frequency and pre-treatment KPS score were the influencing factors of DC-CIK in the treatment of renal cell carcinoma(P<0.05).Multivariate analysis showed that TNM staging was an independent prognostic factor.The second part of the research results:1.Compared with the control group,the expression of p NF-κB protein in DC of gastric cancer patients increased after the action of TLR8 agonist VTX-2337.2.The expression of DC surface maturation markers HLA-DR,CD11 C,CD80,CD86,CD54 and CD83 was up-regulated.The expression of IL-12 and TNF-α in the supernatant of the experimental group was higher than that of the control group.4.DC-T lymphocyte co-culture,there was no significant difference in the expression of HLA-DRCD3 and CD28 in the experimental group.The expression of Lnc-DC in normal human DC was higher than that in gastric cancer patients(P<0.05).The amount of Lnc-DC expression in the agonist group was not significantly different from that in the control group. |
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