Objective To analyse retrospectively the clinical efficacy and prognostic factors of arterial intervention-al therapy combined with epidermal growth factor receptor (EGFR) and tyrosine kinase inhibitors (TKI) erlotinib (erlotinib) on non-small cell lung cancer (NSCLC) patient with brain metastasis. Methods A total of 45 NSCLC patients with brain metastasis were underwent infusion chemotherapy two-six cycles by selective bronchial artery or intracranial arterial. Erlo-tinib (150 mg, 1/d) was used simultaneously or sequentially with the infusion chemotherapy. The clinical efficacy was as-sessed every two cycles or when the disease got progressed. The progression-free survival (PES) and overall survival (OS) were recorded from the follow up data. Results All the patients received at least two cycles of treatment. The median num-ber of cycles was 3 (range 2-6 cycles). The results were as follows:complete remission (CR) in 7 cases (15.56%), partial re-mission (PR) 12 cases (26.67%), stable (SD) 16 cases (35.56%) and progression (PD) 10 cases (22.22%). The objective re-sponse rate (ORR, CR+PR) and disease control rate (DCR, CR+PR+SD) were 42.22%and 77.78%respectively. Patients in this study were followed up for 19 months (6-45 months), with the median PFS time 11.00 months,the median OS time 17.00 months. The univariate analysis showed that patients with low PS score had longer PFS and OS than those of patients with higher PS score. There were 53 adverse events during the treatment. No serious adverse reactions of drugs were found in patients. Conclusion The arterial interventional therapy combined with erlotinib showed a better short-term effect and pro-longed survival time, and with mild side effects.

There exists a population of myeloid-origin cells that are associated with tumor immune escape in cancer patients,commonly termed as myeloid derived suppressor cells(MDSCs).M DSCs accumulate in the blood,lymph nodes,bone marrow,and inhibit both adptive and innate immunity.Different suppressive mechanisms are used by MDSCs to block tumor immunity.Reducing the numbers of MDSCs or inhibiting the suppressive pathway conducted by MDSCs will bring new highlight to biotherapy in tumor treatment.

Radiation could induce DNA damage,cell death,and changes of tumor phenotype and tumor microenvironment leading to the regulation of immune response.Immune checkpoint signaling pathways are involved in the immune tolerance of anti-microorganism responses and thus limit tissue damage.In the anti-tumor immune response,these pathways are associated with anti-functional activation of specific cytotoxic T cells and also enhance the inhibition effect of immune response,which always result in immune escape.Blockade of the immune checkpoint signaling pathways benefits to the anti-tumor inmune responses and could delay tumor progress.As a result,the combination treatment of radiotherapy and immune checkpoint biockade has attracted more attentions in clinical application.This paper reviews the recent research progresses in the radiation effect of immune system,the regulation of immune checkpoints and the combination treatment of radiotherapy and immune checkpoint blockade in tumor therapy,trying to arouse some new clues in cancer therapy.

Recently, it is reported that regulatory T cells (Tregs) can be reprogrammed into a novel population [interleu?kin (IL)-17+Foxp3+T cells] phenotypically and functionally resembling Th17 cells under complicated cytokine circumstanc?es. IL-17+Foxp3+T cells are characterized by production of IL-17 and expression of retinoic acid receptor related orphan re?ceptor (ROR)γt, demonstrating dual functions in immune response and providing novel insight into the interconnection be?tween Tregs and Th17 cells. In this review, we lay emphasis on the phenotype features, origination, differentiation and the pleiotropic functions of IL-17+Foxp3+T cells. Furthermore, we summarized the functions of IL-17+Foxp3+T cells in inflam?matory disease and tumor microenvironment.

Indoleamine 2,3-dioxygenase (IDO) is known as an endogenous immunosuppressive enzyme which plays a significant role in the process of tumor.IDO is not only found in tumor cells but also detected in dendritic cell (DC) in tumor microenvironment,which participates in the formation of tumor immune tolerance through expressing IDO enzyme.Signal transducer and activator of transcription (STAT) is the main signal protein family which participates in the IDO transcriptional regulation of DC.It is necessary to detail the signaling pathway in regulating IDO expression,which will help us develop high specific and more active IDO inhibitors and provide new options for anti-cancer targeted therapy.

Objective: This study aims to investigate the correlation between the expression of FoxP3, TGF-β1, and epitheli-al-mesenchymal transition (EMT) in breast cancer and to determine the clinical significance of FoxP3. Methods: The expression of FoxP3, TGF-β1, E-Cadherin, N-Cadherin, Vimentin, and Fibronectin protein were detected in the cancer cells of 74 cases with breast carcinoma via immunohistochemistry. The correlation of FoxP3 protein with clinico-pathologic features of breast carcinoma and the re-lationships among the expressions of FoxP3, TGF-β1, and epithelial-mesenchymal transition (EMT) were analyzed. Results:The ex-pression rates of FoxP3, TGF-β1, and EMT are 36.5%(27/74), 39.2%(29/74), and 40.5%(30/74), respectively. The FoxP3 protein ex-pression in breast cancer is correlated with lymph node metastasis (P<0.05) but not with other clinico-pathological features (P>0.05). The expression of FoxP3 is also correlated with the expression of TGF-β1. Furthermore, TGF-β1 can induce EMT (P<0.05). Conclu-sion:The expression of FoxP3 is correlated with lymph node metastasis and EMT in breast cancer. Therefore, FoxP3 may be a marker for predicting metastasis.

Objective:Analyze the influence of hematopoietic stem cell mobilization on circulating endothelial cells (CECs) and circulating endothelial precursors (CEPs).Methods:CECs and CEPs were enumerated in 68 tumor patients and 15 healthy controls by 3-color flow cytometry. 11 cases underwent PBSC (peripheral blood stem cell) mobilization by combination chemotherapy and G-CSF (granulocyte colony-stimulating factor).Results:CECs and CEPs in tumor patients were 0.378%?0.103% and 0.059%?0.013% respectively,which were higher than that of normal controls.CECs/CEPs in peripheral blood (PB) were increased after G-CSF mobilization.Conclusion:Hematopoietic and endothelial progenitors can be mobilized into the PB by treatment with growth factor G-CSF.

Objective:To observe ability of DC vaccine transfected with tumor cell total RNA to induce specific antitumor immunity in lung cancer patients in vitro.Methods:DCs were generated from lung cancer patients' peripheral blood mononuclear cells(PBMC).Total RNA was isolated from lung cancer tumor cell line Calu-6 by Trizol.Autologous DCs transfected with Calu-6 total RNA by liposome were used to induce specific CTL proliferation.Specific cytotoxicity and IFN-? secretion were measured by LDH assay and ELISA method.Results:Transfected DCs exhibited dramatically increased expression of specific membrane markers and function-associated molecules,and were more potent in stimulating allogenous or autologous T cell proliferation than that of control DCs.Specific CTLs induced by transfected DCs showed higher cytotoxicity than LAK against Calu-6 antigens positive target cells.When sensitized lymphocytes were restimulated by transfected DCs again,IFN-? secretion enhanced significantly.Conclusion:Lung cancer patient's autologous DCs transfected with tumor total RNA are effective vaccines in stimulating specific antitumor T-cell immunity in vitro.

Objective: To investigate the expression of recombinant human intedeukin-18 (hIL-18) in 3.7 L fermenter with the constructed engineer train Pichia pastoris X-33/hIL-18, and the procedures of expression and purification thereof.Methods: The train X-33/hIL-18 was inoculated in BMGY medium and then inoculated into the fermenter until the A600 of the culture reached about 6. The supernatant of fermentation was isolated and purified with centrifugal fiher devices, hydrophobic chromatography column and anion exchange chromatography column. Results: The recombinant hIL-18 was expressed in 3.7 L fermenter with batch feed methanol and the concentration reached 202 mg/L. After the purification, the purity could be more than 97%. The recombinant hIL-18 was shown to induce interferon-gamma (IFN-γ) production by human peripheral blood mononuclear cells (PBMCs), and enhanced NK cell cytotoxicity synergistically with IL-2. Conclusion: A great deal of the recombinant hIL-18 with higher purity could be harvested by Pichiapastoris expression system. This study showed a new potential for further study of its function and activities.

Objective: To analyze the circulating endothelial cells (CECs) and circulating endothelial precursors (CEPs) in peripheral blood of tumor patients. Methods: CECs and CEPs were enumerated in 57 tumor patients and 15 healthy controls by 3-color flow cytometry. The serum level of angiogenesis related cytokines(VEGF, bFGF)was determined by ELISA method. Results: In tumor patients, mean value of CECs and CEPs was (0.378?0.047)% and (0.059?0.013)% respectively. The serum level of VEGF and bFGF were (295.58?59.56) ng/L and (28.73?7.40) ng/L. The amount of CECs/CEPs positively correlated with the serum level of VEGF and bFGF. Conclusions: The CECs/CEPs and serum level of VEGF and bFGF of tumor patients was higher than those of normal controls. VEGF and bFGF may participate into the course of endothelial progenitors mobilization.