Vaccination with immature dendritic cells combined with CD40mAb induces protective immunity against B lymphoma in hu-SCID mice

Ge, Yan; Xiang, Hong; Zhang, Xueguang

doi:10.1016/j.biopha.2010.01.004

Cited by 6 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peripheral blood mononuclear cells (PBMCs) were isolated using density-gradient-centrifugation-(Ficoll), and the activation of T cells was performed as previously described [27, 28]. Briefly, PBMCs were isolated according to the manufacturer’s instructions and then cultured in RPMI 1640 and 10% FBS overnight.…”

Section: Methodsmentioning

confidence: 99%

EGFR-TKI resistance promotes immune escape in lung cancer via increased PD-L1 expression

et al. 2019

View full text Add to dashboard Cite

BackgroundThe ATLANTIC trial reported that higher PD-L1 expression in tumors was involved in a higher objective response in patients with EGFR+/ALK+ non-small cell lung cancer (NSCLC), indicating the possibility of anti-PD-1/PD-L1 therapy as a third-line (or later) treatment for advanced NSCLC. Therefore, the determination of status and regulatory mechanisms of PD-L1 in EGFR mutant NSCLC before and after acquired EGFR-TKIs resistance are meaningful.MethodsThe correlation among PD-L1, c-MET, and HGF was analyzed based on TCGA datasheets and paired NSCLC specimens before and after acquired EGFR-TKI resistance. EGFR-TKI resistant NSCLC cells with three well-known mechanisms, c-MET amplification, hepatocyte growth factor (HGF), and EGFR-T790M, were investigated to determinate PD-L1 expression status and immune escape ability. PD-L1-deleted EGFR-TKIs sensitive and resistant cells were used to evaluate the immune escape ability of tumors in mice xenograft models.ResultsPositive correlations were found among PD-L1, c-MET, and HGF, based on TCGA datasheets and paired NSCLC specimens. Moreover, the above three resistant mechanisms increased PD-L1 expression and attenuated activation and cytotoxicity of lymphocytes in vitro and in vivo, and downregulation of PD-L1 partially restored the cytotoxicity of lymphocytes. Both MAPK and PI3K pathways were involved in the three types of resistance mechanism-induced PD-L1 overexpression, whereas the NF-kappa B pathway was only involved in T790M-induced PD-L1 expression.ConclusionsHGF, MET-amplification, and EGFR-T790M upregulate PD-L1 expression in NSCLC and promote the immune escape of tumor cells through different mechanisms.

show abstract

Section: Methodsmentioning

confidence: 99%

EGFR-TKI resistance promotes immune escape in lung cancer via increased PD-L1 expression

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Sato and collaborators [93] developed this model to define the role of the complement system in the efficacy of an optimized variant of rituximab. In another example, human Daudi cells were implanted into SCID mice that were reconstituted with human peripheral blood leukocytes to assess the efficacy of a vaccine composed of immature dendritic cells and antihuman CD40 mAb [94]. This study demonstrated the rate at which activated CD8 + cytotoxic T lymphocytes infiltrate Burkitt lymphomas and the high level at which these cells secrete IFN γ after the injection of this vaccine.…”

Section: Models To Analyze the Efficacy Of New Therapiesmentioning

confidence: 99%

Murine Models of B-Cell Lymphomas: Promising Tools for Designing Cancer Therapies

Donnou

Galand

Touitou

et al. 2012

Advances in Hematology

View full text Add to dashboard Cite

Human B-cell lymphomas, the fourth most common hematologic malignancy, are currently the subject of extensive research. The limited accessibility of biopsies, the heterogeneity among patients, and the subtypes of lymphomas have necessitated the development of animal models to decipher immune escape mechanisms and design new therapies. Here, we summarize the cell lines and murine models used to study lymphomagenesis, the lymphoma microenvironment, and the efficacy of new therapies. These data allow us to understand the role of the immune system in the fight against tumors. Exploring the advantages and limitations of immunocompetent versus immunodeficient models improves our understanding of the molecular and cellular mechanisms of tumor genesis and development as well as the fundamental processes governing the interaction of tumors and their host tissues. We posit that these basic preclinical investigations will open up new and promising approaches to designing better therapies.

show abstract

“…The mice had constant access to food and water. The SCID-hu model of pancreatic cancer was established as previously described (21). In brief, hemocytopoiesis in SCID mice was inhibited by administration of cerebrotendinous xanthomatosis at 40 mg/kg/d.…”

Section: Methodsmentioning

confidence: 99%

Lentivirus‑mediated RNA interference targeting programmed death receptor ligand�1 increases the immunologic anti‑tumor effect of dendritic cell vaccination against pancreatic cancer in SCID‑hu mice

et al. 2019

View full text Add to dashboard Cite

Programmed death receptor ligand 1 (PD-L1), which belongs to the B7 family, is overexpressed in a variety of human cancer types and serves a crucial role in immune escape by malignant cells. Programmed death receptor 1 (PD-1) is a specific PD-L1 receptor. PD-1/PD-L1 signaling inhibits the antitumor effects of dendritic cell (DC) immunization for tumor treatment. The aim of the present study was to determine whether inhibiting PD-L1 may increase the immunologic anti-tumor effect of dendritic cells against pancreatic cancer. In the present study, PD-L1 levels in non-cancerous and malignant tissue samples were compared, and the impact of PD-L1 downregulation on human pancreatic cancer PaTu8988 cells was determined by lentivirus-based RNA interference and DC immunotherapy. PD-L1 expression in pancreatic specimens was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. PaTu8988 cells expressing reduced levels of PD-L1 were generated by lentivirus-based knockdown to assess the mechanism by which the inhibition of PD-L1 signaling in DC immunization affects therapeutic outcomes in pancreatic cancer-bearing SCID-hu mice. PD-L1 levels were markedly elevated in pancreatic adenocarcinoma samples compared with in non-cancerous tissue. PD-L1 silencing in pancreatic adenocarcinoma cells resulted in improved treatment outcomes of DC immunization in vitro and in vivo compared with traditional DC immunization. PD-L1 silencing enhances the antitumor response of cytotoxic T cells by increasing interferon γ production in vitro . In vivo , this method prevented tumor growth and lung metastasis, and prolonged survival in the SCID-hu model. In conclusion, the results of the present study suggested that suppressing PD-L1 in malignant cells during DC immunization may be a useful tool for immunotherapy in pancreatic adenocarcinoma.

show abstract

Vaccination with immature dendritic cells combined with CD40mAb induces protective immunity against B lymphoma in hu-SCID mice

Cited by 6 publications

References 25 publications

EGFR-TKI resistance promotes immune escape in lung cancer via increased PD-L1 expression

EGFR-TKI resistance promotes immune escape in lung cancer via increased PD-L1 expression

Murine Models of B-Cell Lymphomas: Promising Tools for Designing Cancer Therapies

Lentivirus‑mediated RNA interference targeting programmed death receptor ligand�1 increases the immunologic anti‑tumor effect of dendritic cell vaccination against pancreatic cancer in SCID‑hu mice

Contact Info

Product

Resources

About