TGFβ1 Expression In Tumor Tissue And Body Fluid Of TCC Patients And Its Effects On Topical And Systemic Cellular Immunity

Research works in malignant glioma, leukemia and pancreas carcinoma had shown that the immune functins of cancer patients were usually impaired to some extent. Further study indicated immunosuppressive cytokines secreted by tumor cells were the cause of such defects. As one of the most important negative regulation factors in the cytokine network of immune system, TGF ?1 was confirmed to be involved in the immune suppression observed in cancer patients, promoting tumor growth by inhibiting immune surveillance. Studys indicated that immune defects also existed in transitional cell carcinoma (TCC) patients. Expression of TGF P 1 in tumor tissue and body fluid in TCC patients was reported to be enhanced significantly. However, no studies about the relation between TGF P 1 level and immune defects in TCC patients has been presented so far. Clarifying the role of TGF 3 1 in the topical and systemic defects of cellular immunity will conduce to immunotherapy for TCC and significantly improve the curative effect.We determined the level of TGF 3 1 expression in the sera and paraffin-embedded specimens of 58 TCC patients by means of immuno-histochemistry and ELISA ,then classified the tumor infiltrating immune cells with immunohistochemistry. we further determined the effect of patiens' sera on the proliferation of PBMC from healthy controls with PHA stimulated lymphocyte proliferation test. With TG? & 1 function blocking antiboday we could determine whether TGF3 1 in patients" serum played a role in affecting PBMC proliferation. We further correlated the expression of TGF 3 1 in tumor tissue and the density of tumor infiltrating immune cells, the concentration of TGF P 1 in patients' sera and the proliferation rate of PBMC culturec with patient' sera. It was our attempt to clarify the relationship between TGF 3 1 and the topical/systemic cellular immunity defects observed in TCC patients with the methods mentioned above.The results from experiment I indicated that the TGF 3 1 expression in tumor cell was significantly higher than that in normal epithelia. With the progression of tumor stage and grade, the TGF 0 1-4-expression decreased significantly. It seemed that TGF3 1 expression was more closely correlated with tumor stage. Only latent TGF P 1 could be detected in serum. The level of serum TGF 3 1 in TCC patients was significantly higher than that of normal control. With tumor stage and grade progression, the concentration of serum TGF3 1 decreased significantly. In patients with lymph node metastasis the level of serum TGF3 1 was below normal level. The TGF3 1 expression in tumor cell and the concentration of serum TGF3 1 correlated with each other positively, but TGF 3 1 secreted from tumor cell might not be the direct cause of the change in the level of serum TGF 3 1. Only latent TGF3 1 could be detected in urine. The concentration of TGF 3 1 in patiests' urine was singnificantly lower than that in normal control. No correlation was found between the concentration of urine TGF3 1 and tumor stage or grade. It could be inferred that TGF3 1 is a negative regulation factor for tumor cell proliferation. TGF 3 1 expression in normal epithelium is important in maintaining the homeostasis of epithelial proliferation. Decreased TGF3 1 expression contributes to tumor cell proliferation. Elevated level of serum TGF 3 1 might lead to serious impairment to patient's immune function. Decreased level of urine TGF3 1 might also promote TCC growth.The results from experiment II indicated that TGF 3 1 could strongly inhibit PBMC proliferaion. Compared with normal serum, sera from early TCC patients inhibited PBMC proliferation. The inhibitory effect decreased with tumor progression. Sera from patient with lymph node metastasis instead promoted PBMC proliferation. The TGF 3 1 concentration and PBMC proliferation rate correlated with each other inversely, suggesting elevated serum TGF3 1 level might be the cause of decreased PBMC proliferation. Functional blocking test further confirmed that serum TGF 3 1 was the m...