Jiangsu Engineering Research Center for Tumor Immunotherapy

Changzhou, China

Jiangsu Engineering Research Center for Tumor Immunotherapy

Changzhou, China
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Wang X.L.,Soochow University of China | Jiang J.T.,Soochow University of China | Jiang J.T.,Jiangsu Engineering Research Center for Tumor Immunotherapy | Wu C.P.,Soochow University of China | Wu C.P.,Jiangsu Engineering Research Center for Tumor Immunotherapy
Genetics and Molecular Research | Year: 2016

Tumor-associated macrophages (TAMs), which play a crucial role in the tumor microenvironment, can be divided into M1 and M2 phenotypes, these phenotypes may exert opposite effects on the prognoses of patients with gastric cancer (GC). The association between TAMs and GC is contentious. Thus, a meta-analysis of 12 studies (incorporating 1388 patients) retrieved from the Cochrane Library, PubMed, and Embase databases was conducted in order to evaluate the relationship between TAMs and GC prognosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled to explore the effect of these cells on survival of GC patients. Our results implied that high total TAM infiltration levels correspond to worse overall survival (OS) in patients with GC (HR = 1.70, 95%CI = 1.39-2.09; P < 0.001), and a similar result was observed in relation to M2 macrophage infiltration (HR = 1.71, 95%CI = 1.19-2.45; P = 0.004). In contrast, elevated M1 macrophage density in GC patients was associated with better OS (HR = 0.46, 95%CI = 0.33-0.65; P < 0.001). This meta-analysis showed that the numbers of infiltrating M2 macrophages and total TAMs might be negative prognostic factors for patients with GC, while M1 macrophage infiltration may be associated with a favorable survival rate. © 2016 The Authors.

Ji M.,Soochow University of China | Ji M.,Jiangsu Engineering Research Center for Tumor Immunotherapy | Liu Y.,Soochow University of China | Li Q.,Soochow University of China | And 9 more authors.
Cancer Biology and Therapy | Year: 2016

This study was aimed to detect the correlation among EGFR/KRAS status and PD-1/PD-L1 expression in non-small-cell lung cancer (NSCLC) patients. PD-1 and PD-L1 expressions were detected by immunohistochemistry in 100 surgically resected lung adenocarcinoma tissues and were statistically correlated with clinicopathological characteristics including EGFR and KRAS statuses. Besides, the overall survival (OS) times were analyzed. There was a statistical significances between PD-1 expression in tumor and KRAS status (P = 0.043), with a higher mutation rate in with lower PD-1 expression patients. There was a statistical significance between PD-L1 expression in tumor and EGFR status (P = 0.012), with a higher mutation rate in patients with lower PD-L1 expression. The OS of patients with EGFR mutation was significantly longer than those without EGFR mutation. The OS of patients with lower PD-L1 in tumor was significantly longer than those with higher PD-L1 expression. We found negative associations between PD-L1 expression in tumor and mutated EGFR status, as well as between PD-1 expression in tumor and mutated KRAS status. © 2016 Taylor & Francis Group, LLC

Hu W.,Soochow University of China | Hu W.,Jiangsu Engineering Research Center for Tumor Immunotherapy | Li X.,Soochow University of China | Li X.,Jiangsu Engineering Research Center for Tumor Immunotherapy | And 6 more authors.
Clinical and Translational Oncology | Year: 2016

Tumor-associated macrophages (TAMs) are major component of leukocytic infiltrate of tumors and play important roles in progression and regression of tumors. Tumor microenvironment determines the mutual conversion between M1 and M2 macrophages. In many kinds of tumors, M2 type macrophages are of the majority in TAMs and promote tumor progression and metastasis. The dynamic balance and interaction between TAMs and tumor cells have important effects on the occurrence and development of tumor. TAMs in malignant tumors are useful for clinical diagnosis and may provide a novel target for cancer treatment. © 2015, Federación de Sociedades Españolas de Oncología (FESEO).

Shi L.,Soochow University of China | Shi L.,Jiangsu Engineering Research Center for Tumor Immunotherapy | Li X.,Soochow University of China | Li X.,Jiangsu Engineering Research Center for Tumor Immunotherapy | And 17 more authors.
Radiotherapy and Oncology | Year: 2016

Background and purpose This trial evaluated the efficacy and safety of CT guided 125I-seed implantation (CTII) plus chemotherapy with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment for locally recurrent rectal cancer (LRRC). Material and methods Patients with LRRC who received one prior chemotherapy regimen were enrolled and divided randomly assigned to FOLFORI alone (Arm A) and FOLFORI plus CTII (Arm B). The primary endpoint was local control time (LCT). Overall survival (OS) and treatment related adverse events (TRAEs) were also observed. Results Fifty-seven patients were enrolled from October 2008 and December 2014. Twenty-seven were assigned into Arm A and 30 into Arm B. The overall response rate of locally recurrent tumor was improved to 100% in Arm B versus 29.6% in Arm A (P < 0.001). A significant longer LCT was observed in Arm A (P < 0.001); median LCT was 12 months in Arm B versus 4 months in Arm A. A borderline significant improvement in OS was also observed in Arm B (P = 0.0464); median OS was 25 months in Arm B versus 19 months in Arm A. For patients without distant metastases, median OS was 37 months in Arm B versus 21 months in Arm A (P = 0.0101). For patients with (neo)adjuvant radiotherapy (ART), a longer LCT and OS were also found in Arm B (P < 0.001 and P = 0.0217, respectively). TRAEs were not serious generally. There was no statistically significant difference in treatment related toxicity between Arm A and B both for all patients and patients receiving ART. Conclusions CTII plus FOLFIRI improves the LCT with tolerable toxicities as a second-line treatment in patients with local recurrent rectal cancer, and is helpful to prolong the OS, particularly in patients without distant metastases or with a history of radiotherapy. © 2015 Elsevier Ireland Ltd.

Shi L.,SoochowUniversity | Shi L.,Soochow University of China | Shi L.,Jiangsu Engineering Research Center for Tumor Immunotherapy | Chen L.,SoochowUniversity | And 22 more authors.
Clinical Cancer Research | Year: 2016

Purpose: Radiofrequency ablation (RFA) has been shown to elicit tumor-specific T-cell immune responses, but is not sufficient to prevent cancer progression. Here, we investigated immunesuppressive mechanisms limiting the efficacy of RFA. Experimental Design: We performed a retrospective case-controlled study on patients with synchronous colorectal cancer liver metastases who had received primary tumor resection with or without preoperative RFA for liver metastases. Tumor-infiltrating T cells and tumoral PD-L1 expression in human colorectal cancer tissues were analyzed by immunohistochemistry. T-cell immune responses and PD-1/PD-L1 expression were also characterized in an RFA mouse model. In addition, the combined effect of RAF and PD-1 blockade was evaluated in the mouse RFA model. Results: We found that RFA treatment of liver metastases increased not only T-cell infiltration, but also PD-L1 expression in primary humancolorectal tumors. Using mouse tumor models, we demonstrated that RFA treatment of one tumor initially enhanced a strong T-cell-mediated immune response in tumor. Nevertheless, tumor quickly overcame the immune responses by inhibiting the function of CD8+ and CD4+ T cells, driving a shift to higher regulatory T-cell to Teff ratio, and upregulating PD-L1/ PD-1 expression. Furthermore, we established that the combined therapy of RFA and anti-PD-1 antibodies significantly enhanced T-cell immune responses, resulting in stronger antitumor immunity and prolonged survival. Conclusions: The PD-L1-PD-1 axis plays a critical role in dampening RFA-induced antitumor immune responses, and this study provides a strong rationale for combining RFA and the PD-L1/PD-1 blockade in the clinical setting. © 2015 American Association for Cancer Research.

Wu C.,Soochow University of China | Wu C.,Jiangsu Engineering Research Center for Tumor Immunotherapy | Zheng X.,Soochow University of China | Zheng X.,Jiangsu Engineering Research Center for Tumor Immunotherapy | And 18 more authors.
Oncotarget | Year: 2016

B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) gene plays important roles in gastric cancer, but the epigenetic regulatory mechanism by microRNA (miRNA) and the functional significance of Bmi-1 inhibition in gastric cancer remains elusive. In this study, we systematically investigated the functional roles of miRNA mediated Bmi-1 suppression in gastric cancer. Our results show that the expression of miR-15a is significantly reduced in gastric cancer and the protein expression levels of Bmi-1 are inversely correlated with miR-15a (P = 0.034) in gastric cancer patient samples. Functional studies revealed that ectopic expression of miR-15a decreased Bmi-1 in gastric cancer cell lines with reduced proliferation and tumor invasion. High levels of Bmi-1 in gastric cancer patients are significantly associated with better overall survival (P = 0.024) based on the Kaplan-Meier survival analysis.

Liu J.,Soochow University of China | Liu J.,Jiangsu Engineering Research Center for Tumor Immunotherapy | Wang H.,Soochow University of China | Xie J.,Soochow University of China | And 2 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2016

Neural fibrolipoma is a kind of benign tumor comprised of hypertrophied fibrofatty tissue with intermixed nerve tissue. Here we report one case of neural fibrolipoma with extensive calcification and ossification on the left neck, which has not been reported in the literature. Based on the literature of neural fibrolipoma, the clinical, pathological characteristics and treatment modalities of this rare tumor type are discussed.

Li X.,Soochow University of China | Li X.,Jiangsu Engineering Research Center for Tumor Immunotherapy | Hu W.,Soochow University of China | Hu W.,Jiangsu Engineering Research Center for Tumor Immunotherapy | And 13 more authors.
Acta Oncologica | Year: 2015

Background. Immunotherapy with immune checkpoint inhibitors has emerged as promising treatment modality for cancer based on the success of anti-CTLA-4 and -PD-1/PD-L1 antibodies. LAG-3 and TIM-3 are two new immune checkpoints. The aim of this work is to review the role and application of LAG-3 and TIM-3 for cancer immunotherapy.Material and methods. Literatures were searched and collected in Medline/PubMed.Results. LAG-3 is presented as a CD4 homolog type I transmembrane protein which binds MHC class II molecules. LAG-3 negatively regulates T cell proliferation, homeostasis and function. IMP321 is formed of an extracellular portion of human LAG-3 fused to the Fc fraction of human IgG1 and has shown increased T cell responses and tolerability in phase I studies on advanced renal cell cancer. When combined with paclitaxel, IMP321 has exerted immune enhancement and tumor inhibition with no significant IMP321-related adverse events. TIM-3 belongs to the TIM family and mainly negatively regulates Th1 immunity. The TIM-3/galectin-9 pathway contributes to the suppressive tumor microenvironment. TIM-3 overexpression is associated with poor prognosis in a variety of cancers. Both LAG-3 and TIM-3 are coexpressed with other immune checkpoints. The application of LAG-3 or TIM-3 does play an important role in anti-tumor responses, and maybe better when combing with anti-CTLA-4 and anti-PD-1/L1 antibodies.Conclusions. These two immune checkpoints play crucial roles in cancer development and may be used in future clinical practice of cancer therapy. © 2015 © 2015 Informa Healthcare.

Du P.,Soochow University of China | Du P.,Jiangsu Engineering Research Center for Tumor Immunotherapy | Du P.,Peoples Hospital of Gansu Province | Xiong R.,Soochow University of China | And 6 more authors.
Journal of Immunology Research | Year: 2016

T cells play an important role in antitumor immunity, and the T cell immunoglobulin domain and the mucin domain protein-1 (TIM-1) on its surface, as a costimulatory molecule, has a strong regulatory effect on T cells. TIM-1 can regulate and enhance type 1 immune response of tumor association. Therefore, TIM-1 costimulatory pathways may be a promising therapeutic target in future tumor immunotherapy. This review describes the immune regulation and antitumor effect of TIM-1. © 2016 Peng Du et al.

PubMed | Jiangsu Engineering Research Center for Tumor Immunotherapy and Soochow University of China
Type: | Journal: Oncotarget | Year: 2016

IL-1 is an essential factor of inflammation initiation, and it also promotes malignant transformation, indicating its tumorigenic property. We aimed to investigate the correlation between IL-1 and miR-144-3p as well as their prognostic values in LUAD and LUSC patients.The IL-1 level in both LUAD and LUSC patients was significantly higher than that of healthy donors (P < 0.001). In both populations, patients with low IL-1 level had better prognosis than high IL-1 level (P < 0.001 and P = 0.010, respectively). In A549 cells, miR-144 showed the biggest expression change (-4.38 fold) after IL-1 exposure. In LUAD patients, a negative correlation was detected between IL-1 and miR-144-3p (r = -0.540, P < 0.001) and the high miR-144-3p group had better prognosis (P = 0.003), which was validated by TCGA data. Clinical stage, IL-1 and miR-144-3p were independent risk factors in LUAD patients. In vitro, IL-1 and miR-144-3p antagomir could enhance proliferation and miR-144-3p mimics would attenuate the promoting effect of IL-1.ELISA and qRT-PCR were applied respectively to detected cytokines and miR-144-3p in 129 LUAD, 54 LUSC and 40 healthy donors. Moreover, miRNA array was carried out for miRNA profiling. TCGA database was employed for validation, and follow up data were collected for prognosis evaluation. MTT assay and western-blot were carried out for proliferation evaluation.In LUAD patients, the serum IL-1 level was correlated with miR-144-3p may affect miR-144-3p at transcriptional level. Both of them were independent risk factors for LUAD prognosis. In addition, IL-1 and miR-144-3p might mediate inflammation-promoted tumorigenesis in LUAD patients.

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