A Study On The Roles Of Dendritic Cell In Renal Carcinogenesis

BackgroundMetastatic renal cell cancer (RCC) is a common urinary tract tumor, which has noobvious clinical symptoms and has a very poor prognosis with a median survival ofonly6to12months from the time of diagnosis. There are conventional treatments forRCC including radiotherapy, chemotherapy, and immunotherapy. RCC is among solidtumors with the most abundant blood vessels,so tyrosine kinase inhibitors wereintroduced in the treatment of RCC patients. However, some patients still appeared totumor progression after taking the medicine. Dendritic cells are heterogeneousprofessional antigen-presenting cells that are critical for the initiation of primary T-cellresponses, which are closely associated with the growth of renal cancer.ObjectiveThis study aimed to investigate the roles of dendritic cell in renal carcinogenesis, andto provide theoretical and experimental basis for clinical applications of DC on RCC.Methods1.30cases of RCC paraffin-embedded tissue and surrounding tissues were collectedduring the past3years, and immunohistochemistry was used to detect the expressionof CD11c, MHC-Ⅱ，and CD34. Then the relationship among them were analyzed. 2.22nude mice with human renal cell cancer were randomized into treatment andcontrol evenly. The treatment group received intragastric administration of Sunitinib(80mg/kg) once a day for14days; the control group received an equal volume ofdistilled water. Both groups were observed in terms of tumor growth. Tumor, spleen,peripheral blood, bone marrow, lymphocyte were detected by flow cytometry forexpression of CD11c, CD80, and MHC-II as well as infiltration and maturity of DCs.3. Clinical data of27mRCC patients treated with sunitinib combined with autologousDC and CIK were reviewed retrospectively. Efficacy, quality of life, immunology andsafety of this treatment were ecaluated.Results1. The positive expression rate of CD11c in RCC tissue[(93.08±66.14)‰] was higherthan that in the surrounding tissue [(25.91±12.29)‰]. Expression of MVD in RCCtissue (26.31±11.05) was significantly higher than that in surrounding tissue(12.78±5.49). The permillage of MHC-Ⅱpositive DC in RCCtissue[(9.65±3.61)‰]was significantly lower than that in the surrounding tissue[(17.60±6.26)‰]. There was a negative correlation between the expression of MVDand MHC-Ⅱ; there was no correlation between the expression of MVD and CD11c.Positive expressions of various indicators in RCC tissue were not related to patients’age, sex, and TNM classification.2. In the treatment group, tumor growth was inhibited with54.22%as oncostatic rateand56.07%as regression rate; there is higher DC maturation from peripheral blood,spleen, bone marrow and lower DC infiltration in tumor.3. Follow-up time ranged from4to25months. Out of all the patients, sunitinib wasreduced in1and discontinued in2due to side effect;1patient quit for personal reasons;14patients developed progressive disease. The progression-free survival was4to 19.5months;10patients died from tumor, the overall survival time was6to21months.The median progression-free survival was16months (95%CI12.5-19.5). The overallsurvival was not archived. The efficacy was evaluated according to ResponseEvaluation Criteria in Solid Tumors (RECIST). All the patients received treatment over1cycle. After one course of treatment, among27patients,0had complete remission,4had partial remission,17had stable disease, and6had progressive disease. Theoverall objective response rate and disease control rate were14.8%（4/27）and77.8%(21/27), respectively. Sunitinib and autologous transfusion of DC and CIK improvedthe immune function and quality of life. The major adverse events were fatigue,hand-foot syndrome, hypertension, hypothyroidism, thrombocytopenia, neutropenia,and fever. Most of adverse events were ameliorated by supportive treatment or dosereduction.Conclusions1. In RCC tissue, there were more MVD and DC than in the surrounding tissue, yetthere were less mDC. There was a negative correlation between MVD and thematuration of DC.2. When resisting renal cancer, Sunitinib is likely to improve DC maturation andreduce infiltration of immature DC (imDC) into renal cell carcinoma (RCC).3. Sunitinib combined with autologous DC and CIK may be beneficial in the treatmentof mRCC with accepted toxic reactions, and it may be considered as a new approachfor the comprehensive treatment of RCC.