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1.
Article in Chinese | WPRIM | ID: wpr-796609

ABSTRACT

PD-1/PD-L1 (programmed cell death 1/programmed cell death 1 ligand 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) are currently approved major immune checkpoints. Immune checkpoint inhibitors against them are novel monoclonal antibodies that perform well in a variety of malignancies such as melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma and Hodgkin′s lymphoma. However, with the increasing use of immune checkpoint inhibitors, immune-related adverse events cannot be ignored. The incidence of gastrointestinal toxicity is second only to skin toxicity. In this review, we focused on the mechanisms of these immune checkpoint inhibitors and the characteristics of gastrointestinal toxicity induced by them, and also discussed the clinical management strategies.

2.
Article in Chinese | WPRIM | ID: wpr-792040

ABSTRACT

PD-1 / PD-L1 (programmed cell death 1 / programmed cell death 1 ligand 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) are currently approved major immune checkpoints. Immune checkpoint inhibitors against them are novel monoclonal antibodies that perform well in a variety of malignancies such as melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma and Hodgkin's lympho-ma. However, with the increasing use of immune checkpoint inhibitors, immune-related adverse events can-not be ignored. The incidence of gastrointestinal toxicity is second only to skin toxicity. In this review, we focused on the mechanisms of these immune checkpoint inhibitors and the characteristics of gastrointestinal toxicity induced by them, and also discussed the clinical management strategies.

3.
Article in Chinese | WPRIM | ID: wpr-706856

ABSTRACT

With the clinical applications of new immunotherapies, traditional TNM staging has been unable to meet the clinical needs of curative effect predictions. It is known that the immunological features of the tumor immune microenvironment play important roles in tumor prognosis evaluations. Recently, the immunoscore system, which is based on local immune cell distribution and density, has gradually become an important indicator for prognosis evaluations and has been verified in several tumor researches. Recently, with the application of new mass flow detection and single cell sequencing technologies, the number of immune landscape studies have also been increasing, and new tumor-specific immune cell subsets have been identified. These subtypes not only provide individ-ualized immunotherapy guidelines for patients, but also provide potential new targets for the further development of new immuno-therapy strategies. This review will introduce recent research progress in this field.

4.
Article in Chinese | WPRIM | ID: wpr-691596

ABSTRACT

Chimeric antigen receptor T-cell (CAR-T) is one of the effective methods for treatment of lymphoma. The way to improve the efficacy and control the reverse reactions still needs to be explored further. Several clinical trials have indicated CAR-T could have favorable effects on the B-cell lymphoma patients with controllable reverse reactions. However, antigen loss is a major factor for the acquired resistance to CD19 CAR-T therapy. Other clinical researches, including CD22 for treatment of B-cell lymphoma and CD30 for Hodgkin lymphoma, have increased the efficacy of CAR-T. Moreover, lots of trials have suggested that the patients who received cyclophosphamide or bendamustine plus fludarabine lymphodepletion can get a high effective rate.

5.
Journal of Breast Cancer ; : 150-157, 2018.
Article in English | WPRIM | ID: wpr-714866

ABSTRACT

PURPOSE: The treatment of triple-negative breast cancer (TNBC) remains challenging, due to the absence of estrogen, progesterone, and human epidermal growth factor receptors. This study was designed to evaluate the efficiency and safety of cytokine-induced killer (CIK) cell immunotherapy, following regular chemotherapy, for patients with TNBC. METHODS: A total of 340 patients with postmastectomy TNBC, from January 1, 2010 to June 30, 2014, were included in this retrospective study. Seventy-seven patients received CIK cell immunotherapy, following regular chemotherapy (arm 1), and 263 patients received regular chemotherapy alone (arm 2). The primary aim was overall survival (OS) and disease-free survival (DFS), and the treatment responses and adverse events were also evaluated. RESULTS: The 5-year DFS and OS rates in arm 1 were 77.9% and 94.3%, compared with 69.8% and 85.6% in arm 2, respectively (p=0.159 and p=0.035, respectively). This clearly shows that there was no statistical difference in the 5-year DFS between the two groups. Multivariate analyses of arm 1 indicated that a Karnofsky performance score (KPS) ≥90 and stage I/IIA disease were significantly associated with a prolonged DFS period (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.09–0.74; p=0.012; and HR 0.21; 95% CI, 0.06–0.82; p=0.024, respectively), but a KPS ≥90 and stage I/IIA disease were not independent prognostic factors for OS. Toxicity was mild in patients who received the CIK therapy. CONCLUSION: The data suggested that CIK cell immunotherapy improved the efficiency of regular chemotherapy in patients with TNBC, and the side effects of CIK cell immunotherapy were mild.


Subject(s)
Arm , Cytokine-Induced Killer Cells , Disease-Free Survival , Drug Therapy , Estrogens , Humans , Immunotherapy , Multivariate Analysis , Progesterone , Prognosis , ErbB Receptors , Retrospective Studies , Triple Negative Breast Neoplasms
6.
Article in Chinese | WPRIM | ID: wpr-666281

ABSTRACT

Cancer immunotherapy uses the host′s immune system to mobilize immune cells to rec-ognize and eventually eliminate cancer cells .At present, studies in terms of cancer immunotherapy mainly focus on programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T-lymphocyte-associated protein 4 ( CTLA-4 ) antibody, chimeric antigen receptor T-cell immunotherapy (CAR-T), T cell receptor Immunotherapy (TCR-T), etc.Despite the fact that cancer immunotherapies elicit unprecedented durable responses in clinical therapy , they appear to be ineffective to some patients .In addition, some responders relapse and show resistance to immunotherapies even if their symptoms are re -lieved for a time .Resistance to cancer immunotherapy can be categorized into primary , adaptive and ac-quired, which can occur in every stage during the process of anti-tumor response.In this review, we discuss the known mechanisms of resistance and provide a rationale for the use of combination therapy to overcome resistance.

7.
Article in Chinese | WPRIM | ID: wpr-502324

ABSTRACT

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.

8.
Article in Chinese | WPRIM | ID: wpr-490904

ABSTRACT

Objective To investigate and compare the clinical effects of radiochemotherapy alone or in combination with adoptive immunotherapy with cytokine-induced killer ( CIK) cells in patients with locally advanced non-small cell lung cancer (NSCLC).Methods The clinical data of 125 patients with locally advanced NSCLC who were admitted from 2011 to 2012 and did not undergo surgery were analyzed retrospectively, and among these patients, 102 received radiochemotherapy alone ( control group) , and 23 received radiochemotherapy combined with adoptive immunotherapy with CIK cells ( multimodality therapy group) .The two groups were matched at a ratio of 1:2 using propensity score matching, and the factors considered included tumor stage, radiochemotherapy regimen, and outcome after radiochemotherapy.Then 59 patients ( 22 from the multimodality therapy group and 37 from the control group) were enrolled, and survival and tumor control were compared between the two groups.The Kaplan-Meier method was used to calculate survival rates and the log-rank test was used for survival difference analysis and univariate prognostic analysis.Results The 1-, 2-, and 3-year overall survival ( OS) rates were 73%, 32%, and 16%, respectively, in the control group, and 91%, 59%, and 41%, respectively, in the multimodality therapy group ( P=0.030) .The 1-, 2-, and 3-year progression-free survival rates were 61%, 21%, and 17%, respectively, in the control group, and 45%, 10%, and 10%, respectively, in the multimodality therapy group ( P=0.538) .As for the patients with stage ⅢB NSCLC, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group (47%vs.11%, P=0.026). In the patients receiving sequential chemoradiotherapy, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group ( 46%vs.11%, P=0.003) .As for the patients with squamous cell carcinoma, those in the multimodality therapy group had a significantly higher 3-year distant metastasis-free survival rate than those in the control group ( 73%vs.22%, P=0.029) .The two groups showed similar incidence rates of adverse events, and compared with the control group, the multimodality therapy group had a lower incidence rate of radiation pneumonitis (9%vs.15%, P=0.889) and a higher incidence rate of radiation esophagitis (12%vs.7%, P=0.097).Conclusions Some patients with locally advanced NSCLC can benefit from radiochemotherapy combined with adoptive immunotherapy with CIK cells, but the intended population, timing, and dose safety still need further investigation.

9.
Tianjin Medical Journal ; (12): 1342-1344, 2015.
Article in Chinese | WPRIM | ID: wpr-481503

ABSTRACT

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.

10.
Article in Chinese | WPRIM | ID: wpr-452103

ABSTRACT

Objective:This study aims to investigate the correlation and significance between the expression of P53 and epitheli-al-mesenchymal transition (EMT) in breast cancer. Methods:The expression patterns of P53, Twist, Snail, E-cadherin, N-cadherin, Vi-mentin, and Fibronectin protein were detected via immunohistochemistry in 63 cases with breast carcinoma. The correlation of P53 pro-tein with clinicopathologic features and survival of breast carcinoma, as well as the relationship between the expression of P53 and EMT, was analyzed. Results:The expression rates of P53, Twist, Snail, and EMT are 44.4%(28/63), 54.0%(34/63), 68.3%(43/63), and 41.3%(26/63), respectively. The P53 protein expression is correlated with tumor grade (P0.05). The expression of P53 is also correlated with the expression of Twist and Snail, which are associated with EMT (P<0.05). Multivariate survival analysis reveals that lymph node metastasis, P53, and EMT are independent prognostic factors. Conclu-sion:The expression of P53 is correlated with tumor grade and EMT in breast cancer, which can be used as an independent prognostic factor. Therefore, P53 may be an effective target for breast cancer therapy.

11.
Article in Chinese | WPRIM | ID: wpr-445382

ABSTRACT

Objective:To describe the expression profiling of microRNAs of patients with non-small cell lung cancer. Methods:We reduced the scope of downregulated microRNAs in patients with non-small lung cancer by high throughput microarray based on quantitative real-time PCR (qRT-PCR). In this process, the downregulated microRNAs of non-small cell lung cancer tissues can be de-tected and compared with adjacent healthy lung tissues with relatively small samples. Different microRNA expression levels in non-small cell lung cancer and adjacent healthy lung tissues were verified in a large sample by RT-PCR. Results:A total of 20 types of microRNAs were significantly downregulated in non-small cell lung cancer tissues compared with adjacent healthy lung tissues. These microRNAs were listed as follows: hsa-miR-1; hsa-miR-22; hsa-miR-27a; hsa-miR-27b; hsa-miR-125a-5p; hsa-miR-125b;hsa-miR-142-5p;hsa-miR-143;hsa-miR-148a;hsa-miR-148b;hsa-miR-370;hsa-miR-373;hsa-miR-381;hsa-miR-489;hsa-miR-519a;hsa-miR-376c;hsa-miR-206;hsa-miR-380-5p;hsa-miR-223-5p;and hsa-miR-520c-3p. Among these microRNAs, 13 types were down-regulated in non-small cell lung cancer tissues as verified by RTPCR. These 13 types of microRNAs were listed as follows:hsa-miR-125a-5p; hsa-miR-143; hsa-miR-519a; hsa-miR-223-5p; hsa-miR-1; hsa-miR-520c-3p; hsa-miR-489; hsa-miR-27a;hsa-miR-373; hsa-miR-125b; hsa-miR-27b; hsa-miR-142-5p; and hsa-miR-206. Conclusion: In non-small lung cancer tissue, several kinds of microRNAs were significantly downregulated. Changes in microRNA expressions were significantly associated with tumori-genesis, progression, or other cancer cell functions in non-small cell lung cancer.

12.
Article in Chinese | WPRIM | ID: wpr-443747

ABSTRACT

Aurora-A is a mitotic serine/threonine kinase that is evolutionally conserved and localized at the centrosome. Aurora-A activation is required for mitotic entry, centrosome maturation, and centrosome separation. Aurora-A is frequently amplified and/or over-expressed in breast, ovarian, esophageal, colon, lung, and bladder cancers. Aurora-A has recently become a new target of malignant tumors. The Aurora-A inhibitor can be combined with other chemotherapeutic drugs to provide a new way for cancer treatment. In this study, we review the function and inhibitor of Aurora-A kinase.

13.
Article in Chinese | WPRIM | ID: wpr-439937

ABSTRACT

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 (P0.05). 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.

14.
Article in Chinese | WPRIM | ID: wpr-456505

ABSTRACT

Objective:To highlight the developmental process of 3D cell culture technology system, which is more suitable for isolating and identifying lung cancer stem-like cells than 2D cell culture technology system, and to explore the application of 3D cell cultures in the evaluation of proliferation, apoptosis, invasion, and drug resistance of lung cancer. Methods:Cells (104/well) from the human lung adenocarcinoma cell lines A549 and RPMI 1640 were cultured in complete medium containing 10%fetal bovine serum. Cell suspension was cultured in a BME basal medium. A growth curve was drawn after 7 d of culture. The stem-like cell was identified through a mammosphere culture, drug resistance and invasion assay, and flow cytometry. Data of A549 cells cultured in 3D and 2D tra-ditional cell culture technologies were compared. Results: Cells from the 3D cell culture had higher tumor formation rates [(20.75 ± 0.85) d vs. (60.25 ± 1.49) d, P<0.01)] and tumor sphere formation (28.50%± 1.17%vs. 8.67%± 0.80%, P<0.01) than those from the 2D cell culture. Moreover, cells from 3D cell culture were more invasive and resistant to therapy (58.17%± 2.19%vs. 41.70%±5.81%in 48 h, P<0.01;33.27%±5.76%vs. 27.30%±4.25%in 72 h, P<0.01). Phenotype experimental results demonstrated that the CD44 and CD326 cells were double-positive, whereas the CD24 cell was negative. Conclusion:The proportion of stem-like cells in A549 cell line after 3D cell culture significantly increased compared with 2D cell culture. The 3D cell culture can promote the proliferation of lung cancer stem cells.

15.
Tianjin Medical Journal ; (12): 271-274, 2014.
Article in Chinese | WPRIM | ID: wpr-473466

ABSTRACT

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.

16.
Article in Chinese | WPRIM | ID: wpr-454485

ABSTRACT

Objective:To study the role of FDCs-miR-548m-CDK6 axis on clonogenicity in mantle cell lymphoma. Methods:RT-qPCR and Western blot were used respectively to test the expression of miR-548m and CDK6. Bioinformatics assay was applied to predict the targets of miR-548m, and Western Blot was used to test the expression level of CDK6 after miR-548m overexpression or in-hibition. Luciferase report assay was performed to test whether CDK6 was a direct target of miR-548m. Colony forming assay was used to test the colony forming activity in MCL after overexpression of miR-548m or knockdown of CDK6. Results:Cell adhesion to FDCs induced downregulation of miR-548m and CDK6 expression in MCL. Bioinformatics assay revealed that miR-548m could target the 3'-UTR of CDK6 and that a negative correlation exists between the level of miR-548m and the CDK6 expression. Luciferase report as-say confirmed that miR-548m directly targeted 3'-UTR of CDK6. Colony forming assay showed that overexpression of miR-548m or knockdown of CDK6 significantly suppressed MCL colony formation. Conclusion:This study reveals that FDC-enhanced mantle cell lymphoma clonogenicity is mediated by the miR-548m/CDK6 axis.

17.
Chinese Medical Journal ; (24): 1149-1154, 2014.
Article in English | WPRIM | ID: wpr-253184

ABSTRACT

<p><b>OBJECTIVE</b>To introduce the recent developments in cancer immunoinformatics with an emphasis on the latest trends and future direction.</p><p><b>DATA SOURCES</b>All related articles in this review were searched from PubMed published in English from 1992 to 2013. The search terms were cancer, immunoinformatics, immunological databases, and computational vaccinology.</p><p><b>STUDY SELECTION</b>Original articles and reviews those were related to application of cancer immunoinformatics about tumor basic and clinical research were selected.</p><p><b>RESULTS</b>Cancer immunoinformatics has been widely researched and applied in a series of fields of cancer research, including computational tools for cancer, cancer immunological databases, computational vaccinology, and cancer diagnostic workflows. Furthermore, the improvement of its theory and technology brings an enlightening insight into understanding and researching cancer and helps expound more deep and complete mechanisms of tumorigenesis and progression.</p><p><b>CONCLUSION</b>Cancer immunoinformatics provides promising methods and novel strategies for the discovery and development of tumor basic and clinical research.</p>


Subject(s)
Cancer Vaccines , Therapeutic Uses , Computational Biology , Methods , Humans , Neoplasms , Diagnosis , Allergy and Immunology
18.
Article in Chinese | WPRIM | ID: wpr-440744

ABSTRACT

Malignant pheochromocytomas are rare tumors that arise from chromaffin tissue, and the diagnostic criterion of malig-nancy is based on the development of metastases. In the case a patient suffers the tumor with liver, lung and bone metastases. However, the test results of tumor markers, gastroscopy, chest and abdominal CT, and PET-CT examination are hard to make a definite diagnosis. The patient was finally diagnosed with malignant pheochromocytoma with liver, lung and bone metastases following the needle biopsy of liver and underwent the excision of a right adrenal pheochromocytoma. Therapeutic standard for the malignant pheochromocytomas is not available so far. It is reported that chemotherapeutic CVD regimen (cyclophosphamide, vincristine, and daecarbazine) and suni-tinib may be effectual in the alike cases. The patient received two cycles of CVD and one cycle of sunitinib, nevertheless, slow progres-sion of the disease remained after the treatment. The results of multi-disciplinary treatment have suggested that 131I-MIBG may just be a choice for this patient.

19.
Article in Chinese | WPRIM | ID: wpr-438258

ABSTRACT

Objective:This work aims determine the expression of the neurotensin (NTS) gene in hepatocellular carcinoma (HCC) subgrouping using immunohistochemical staining (IHC) as well as to evaluate the correlation between the activation of NTS/IL-8 pathway in HCC and inflammatory response in microenvironment and epithelial mesenchymal transition (EMT) in cancer and in the prognosis of patients. Methods:Tumor tissues and corresponding adjacent normal tissue were collected from 64 cases of HCC patients. The expression levels of NTS protein and multiple inflammation and EMT-related proteins, including IL-8, VEGF, MMP9, CD68, E-Cadherin,β-Catenin, and Vimentin, were examined in 64 cases of paraffin-embedded HCC tissues using the immunohistochemistry (IHC) staining method. The clinical outcome and overall survival (OS) among 64 cases of HCC patients were compared. Results:We found that the frequency of NTS-expressing tissues among all HCC samples was 17.19%(11/64). Significantly increased IL-8 protein was confirmed in 90.91%of NTS+HCC samples and was positively correlated with the levels of NTS protein in cancer tissues (P=0.036), which implied the dysfunctional activation of NTS/IL-8 pathway in HCC. The levels of VEGF and MMP9 were significantly correlated with the co-expression of NTS and IL-8 in HCC. Evident features of EMT, including decreased membrane expression of E-Cadherin and increased accumulation of cytoplasmicβ-Catemin and Vimentin, were found in NTS+IL-8+samples. The co-expression of NTS and IL-8 in cancer was significantly correlated with the clinical outcomes of patients, as the mortality rate of NTS+IL-8+HCC patients is 2.5-fold higher than that of others after surgery (P=0.022).Accordingly, the OS of NTS+IL-8+HCC patients significantly decreased (24.65±4.45 m vs. 75.79±16.32 m, P=0.013), and these patients are at a higher risk of death at an expected hazard ratio (HR) of 3.457. Conclusion:The NTS/IL-8 pathway is dysfunctionally activated in a subgroup of HCC samples. Highly expressed NTS is associated with increased inflammatory response in microenvironment, enhanced EMT in cancer, and worse prognosis in HCC patients.

20.
Article in Chinese | WPRIM | ID: wpr-438252

ABSTRACT

Objective:To explore the status of STAT3 phosphorylation in myeloid-derived suppressor cells (MDSCs) of breast cancer and its function in the immunosuppressive effect of MDSCs on proliferation and cytokine secretion of T cells. Methods:CCD33+cells were isolated from healthy umbilical cord, blood-derived, peripheral blood mononuclear cells and were co-cultured with breast cancer cell line MDA-MB-231 in vitro using Transwell plates to induce MDSCs. The untreated CD33+cells were used as con-trols. Idoxuridine (IDO) suppressor expression and STAT3 phosphorylation were examined using Western blot assay. The proliferation and cytokine secretion of T cells, which were co-cultured with MDSCs, were determined by methyl thiazol tetrazolium assay and en-zyme-linked immunosorbent assay. 1-MT and JSI-124 were used to investigate the function of IDO and pSTAT3 in MDSC-mediated T cell immunosuppression. Results:The protein levels of IDO and pSTAT3 in MDSCs were significantly upregulated. MDSCs obviously suppressed T-cell proliferation, which was reversed by 1-MT or JSI-124 (P<0.05). MDSCs could promote TGF-βand IL-10 secretions, but could also remarkably inhibit IFN-γsecretion (P<0.05). After incubation with 1-MT or JSI-124, the increase in TGF-βand IL-10, as well as the decrease in IFN-γ, was significantly reversed. Conclusion:The upregulated pSTAT3 induced the IDO increase in MDSCs. JSI-124 can block MDSC-mediated immunosuppressive effect on T cells in breast cancer.

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