| [Background and Aims] Malignant tumor's two most basic characteristics are uncontrolled cell proliferation and metastasis. In recent years, many researches reveal that malignant tumor cell's biological behaviour is associated with many factors.Among these factors, the growth factor and its receptor play the key roles. Since 1990, the molecular targeted therapy which treats the growth factor receptor as the target has attracted worldwide attention. At present, the monoclonal antibodies which is developed according to the patient's receptor,gene combined with the chemoradiation has become one of the most important comprehensive treatments of the tumor. Antitumor mechanism of monoclonal antibody includes:blocking signaling pathway,ADCC role or CDCC role and immune adjustment effect. The EGFR is widely distributed in membrane and high EGFR expression is related to the tumor's high malignance,prone to metastasize,short remission and high recurrence rate. Cetuximab(C225) as the anti-EGFR targeted drug,combined with chemoradiation or monotherapy has achieved very good result in many malignant tumor.As specific antibody,its mechanism is blocking intracellular signaling pathways,then inhibit cancer cell proliferation and induce apoptosis in cancer cells. There are reports indicate that monoclonal antibodies are capable of inducing immune recovery, interfering specific antigen and its ligand binding, which can induce autoimmune response. It has been known that chemotherapy can partly inhibit the cell immunity. But no reports have been published manifested how C225 combined with chemotherapy will affect tumor local immunity. This trial first detected CD8, IL-2,TNF-α, VEGF, TGF-β1.etc expression in tumor tissue of 12 patients before and after using C225 combined with chemotherapy, then analyze the influence of C225 combined with chemotherapy on the immune status of the tumor microenvironment and whether this effect may be related to clinical effecacy. Researches in this area will be able to provide a theoretical basis for a better choice of clinical medicine.[Methods] 12 cancer patients that applied C225 combined with chemotherapy were selected, and their tumor tissue were collected before and after treatment. Tumor tissue was detected by immunohistochemical methods and compared the changes of expression intensity before and after treatment. Detected indicators:CD8, IL-2, TNF-a, VEGF, TGF-β1. Clinical efficacy of 12 patients was evaluated. Paired samples signed ranks test (Wilcoxon paired method) was used to compare the differences of immune parameters expression intensity before and after treatment. Correlativity was analyzed by Spearman correlation analysis. Chi-square test estimation method was used to analyze the change of each index and treatment outcome.[Results]1,The expression intensity of TGF-β1 before and after treatment was not statistically significant, P value>0.05. The relationship between expression intensity of TGF-β1 before and after treatment and efficacy was significantly different, P value=0.05.If expression of TGF-β1 decreased or did not change, the clinical benefit rate was 100%; TGF-β1 expression intensity increased, the clinical benefit rate was 33.33%.2,The expression intensity of CD-8 before and after treatment and the relationship with the effect were not statistically significant, P value>0.05. Compared with before and after treatment, CD8 expression of 7 cases (58%) in 12 patients decreased.3,The expression intensity of IL-2 before and after treatment and the relationship with the effect were not statistically significant, P value>0.05. Compared with before and after treatment, IL-2 expression of 7 cases (58%) in 12 patients decreased. Before treatment, in 3cases IL-2 expressed strongly positive (+++), and 1 case' effect was SD, 2 cases were PR.4,The expression intensity of TNF-αbefore and after treatment and the relationship with the effect were not statistically significant, P value>0.05.Before treatment in 4 cases of PD patients,1 case' expression of TNF-a was weakly positive (+), the other 3 cases were negative. Before treatment, TNF-a expression in 2 cases was strongly positive (+++) and their efficacy was PR.5,The expression intensity of VEGF before and after treatment and the relationship with the effect were not statistically significant, P value>0.05. Compared with before and after treatment, in12 patients 5cases (41.7%) VEGF expression increased.6,The expression intensity of IL-2 before and after treatment and treatment times were significantly negative correlation, Spearman correlation coefficient= -0.585, P values=0.046.Changes of expression of TGF-β1 and the effect was significantly negative correation, Spearman correlation coefficient=-0.684, P values =0.014.The expression intensity of CD8, TNF-a.VEGF and efficacy, treatment times had no significant difference, P values >0.05. Before treatment, expression intensity of TNF-αand IL-2 had significant positive correlation, Spearman correlation coefficient=0.629, P values=0.028. After treatment, expression intensity of TGF-β1 and CD8 had significant negative correlation, Spearman correlation coefficient=-0.664, P values=0.019.[Conclusion]1,The expression intensity of TGF-β1 before and after treatment had no statistically significant. The expression intensity of TGF-β1 was negatively correlation with the effect. If TGF-β1 expression intensity decreased or no change, recent efficacy was good, and TGF-β1 expression intensity increased, recent efficacy was poor. C225 combined with chemotherapy decreased some patients'cellular immune response, some cellular immune response increased.2,Before and after treatment, CD8,IL-2,VEGF,TNF-α. expression intensity were not statistically significant.Their expression intensity and effects had no correlation. The expression intensity changes of CD8,IL-2,VEGF,TNF-αand TGF-β1 had no correlation each other.3,Before and after treatment,IL-2 expression level was negatively correlated with treatment times, Which means the more times of C225 compared with chemotherapy, the lower IL-2 expression intensity would be. This suggests that when treatment times increased, immunosuppression aggravated. 4,Before treatment, the expression of TNF-a and IL-2 were positively correlated. IL-2 may promote TNF-αexpression or they may promote each other. After treatment, expression of TGF-β1 and CD8 were negatively correlated. This suggests that TGF-β1 may inhibit specific cellular immune response through inhibiting T cell proliferation.5,Before treatment, IL-2. TNF-αexpressed a strong positive trend of recent good effecacy; TNF-αexpression was negative or weak expressed a trend of recent poor effecacy. This suggests that initial immune status could be able to predict recent curative effecacy.
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