| Backgrounds and purpose Malignant melanoma is one kind of tumor which is developedfrom melanocytes deriving from neural crest under the influence of many factors. Malignantmelanoma is one of the rare tumors with high-grade malignancy, which accounts for4percentof all the primary skin malignant tumor and the lethality is79percent. Most of the patientsbegin to onset of malignant melanoma in their forties. The median survival time of patientswith metastatic melanoma is about six to nine months and the five-year survival rate is under5percent. The therapeutic effects of traditional surgeon, chemotherapy and radiotherapy onmalignant melanoma are unsatisfactory, so it is deemed as one of the most challenging tumors.The cytokine-induced killer (CIK) cells were found by Schmidt in1991. CIK cells are a groupof heterogenous cells with high-proliferation rates and anti-tumor activities. Under thecircumstance of tumor microenviroment or virus infection, CIK cells can recognize the cellswhich express major histocompatibility complex I antigen MICA and MICB through thenatural killer cell receptors and then kill these cells. Nowadays CIK cells are applied asanti-tumor activated effect cells widely. CIK cells are a group of heterogenous cells mainlycomposed of CD3+CD56+、CD3+CD8+cells in vitro amplication. After the mononuclearcells are separated from peripheral blood, marrow or umbilical cord blood, they are culturedunder many kinds of cytokines in vitro and after a period of time the immunocompotent cellsare attained. This kind of immunocompotent cells can secret many cytokines and ownpowerful anti-tumor activities. Myeloid-derived supressor cells (MDSC) is one kind ofheterogenous suppressor cells deriving from marrow, this kind of cells are immature myeloidcells, most of which locate in the marrow and can be develped into dendrtic cells andmacrophages. Under the effect of cytokines from tumor cells MDSC can be developed intoimmature myeloid cells. MDSC express high density of CD11b and CD33in peripheral bloodand play an immunosuppressive effect in tumor patients. It was showed that MDSC playimmunosuppresive effect through the suppressing the function of T cells, B cells and NK cellsand inducing the production of Treg and then the failure of therapy. Thus it will be of greatsignificance by removal of the suppress effect of MDSC through CIK cells and reconstructionof the anti-tumor immune system in the treatment of malignant melanoma.Through analysis of the mechanism of myeloid-derived suppressor cells (MDSC) and the influence ofcytokine-induced killer cells on MDSC and multiple cytokine in malignant melanoma, thepurpose of this study are as follows:1To observe the clinical efficacy of CIK cells inmalignant melanoma patients;2To analysis the relationship of MDSC and clinical efficacy inmalignant melanoma;3To detect the influences of CIK cells on MDSC in peripheral blood inmalignant melanoma. All these would provide new way and method for the therapy ofmalignant melanoma.Methods Data of the43patients were studied retrospectively, who were diagnosed asreplased/refractory malignant melanoma in the biological treatment department of cancerhospital affiliated to zhengzhou university (primary Henan cancer hospital) from June2009toOctomber2011. The median age was56years old (from29to78years old). All thepatients have no infectious diseases history except three patients with positive hepatitis Bsurface antigen. There are13patients with stage Ⅲ and30with stage Ⅳ. The inclusioncriteria are as follows:①measurable lessions;②life expectancy of at least4months;③Kamofsky score of at least60;④blood routine is normal (white cells≥4.0×109/L,lymphocyte≥0.8×109/L, hemoglobin≥100g/L, platelet≥100×109/L);⑤normal heart, lung,renal and hepatic function;⑥no serious concomitant diseases;⑦CIK therapy of at least4cycles. In addition40healthy volunteers were included, who have no tumor-related diseases,no trauma and infection recently. All the clinical characteristics of the healthy volunteers werematched with the malignant melanoma patients. The patients and the volunteers signed theinformed consent and this study was approved by ethics committee.1.Obtaining of peripheral blood of patients and volunteers.2. detection of MDSC andcytokines by flow cytometry.3. conculation of the survival time of melanoma patients.4. allthe conculations were performed in SPSS17.0. single-sample t-test, independent samples ttest, kaplan-meier survival analysis were used. Inspection level α=0.05and p＜0.05wereassumed to have statistically significance.Results1. The MDSC(CD11b+CD33++、 CD11b+CD33+) level(7.372±3.4104、51.149±14.1659)of malignant melanoma patients before the treatment with CIK cells ishigher than those(1.05±0.34、13.14±4.99，p＜0.05)of healthy volunteers’.2. The MDSC(CD11b+CD33++、 CD11b+CD33+) level(4.702±1.8798、 42.188±17.0488)after treatment of CIK cells was lower significantly than those(7.372±3.4104、51.149±14.1659，p＜0.05)before the treatment of CIK cells in malignantmelanoma patients, but still higher than that of healthy volunteers’.3. The functions of T cells and B cells in malignant melanoma patients (4.605±4.8968、2.902±9.2897)were lower than that of healthy volunteers’(6.078±3.7605、7.710±0.8655，p＜0.05)significantly, but after CIK cells therapy the functions of T and B cells(6.481±7.2186、7.693±9.5124)were improved significantly, and the difference with that of healthy volunteers’was no stastistically significance.4. The median overall survival of the refractory/relapsed malignant melanoma patientswho were treated with CIK cells was11.8months, which is longer than6-8months reported.5. The CBA(IL-2、IFN-γ) numbers before CIK therepy(1698.0±4.7、1470±31.7)is lowerthan those(2460±4.5、1569±34.9，p＜0.05)after treatment of CIK cells.Conclusion:1.The clinical efficacy of CIK is accurate，which is expected to become a new treatmentto recurrent and refractory MM patients.2. There is a correlation between the clinical efficacy of CIK cells and MDSC3. The MDSC in peripheral blood reduced significantly and the immunopotence of T andB cells improved significantly after therapy of CIK cells. |
PDF Full Text Request