Activating anti-CD40 antibodies induce tumour invasion by cytotoxic T-lymphocytes and inhibition of tumour growth in experimental liver cancer

Ryschich, Eduard; Märten, Angela; Schmidt, E.; Linnebacher, Michael; Wentzensen, Nicolas; Eisold, S.; Klar, E.; Büchler, Markus W.; Schmidt, Jan

doi:10.1016/j.ejca.2006.01.024

Cited by 11 publications

(6 citation statements)

References 24 publications

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“…Our results agree with prior studies that suggest an important effect of CD40 on leukocyte migration across endothelial cells and into tumors (55,69). The defect in T-cell migration to the CNS in CD40 Ϫ/Ϫ mice is also consistent with studies on CD4 ϩ T-cell trafficking during experimental autoimmune encephalomyelitis (1,3,26,31,68) and suggest a critical role for CD40-CD40L interactions in the regulation of lymphocyte movement into the CNS.…”

Section: Discussionsupporting

confidence: 83%

CD40-CD40 Ligand Interactions Promote Trafficking of CD8 ⁺ T Cells into the Brain and Protection against West Nile Virus Encephalitis

Sitati¹,

McCandless

Klein

et al. 2007

J Virol

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Recent studies have established a protective role for T cells during primary West Nile virus (WNV) infection. Binding of CD40 by CD40 ligand (CD40L) on activated CD4؉ T cells provides an important costimulatory signal for immunoglobulin class switching, antibody affinity maturation, and priming of CD8 ؉ T-cell responses. We examined here the function of CD40-dependent interactions in limiting primary WNV infection. Compared to congenic wild-type mice, CD40؊/؊ mice uniformly succumbed to WNV infection. Although CD40 ؊/؊ mice produced low levels of WNV-specific immunoglobulin M (IgM) and IgG, viral clearance from the spleen and serum was not altered, and CD8؉ T-cell priming in peripheral lymphoid tissues was normal. Unexpectedly, CD8؉ T-cell trafficking to the central nervous system (CNS) was markedly impaired in CD40 ؊/؊ mice, and this correlated with elevated WNV titers in the CNS and death. In the brains of CD40 ؊/؊ mice, T cells were retained in the perivascular space and did not migrate into the parenchyma, the predominant site of WNV infection. In contrast, in wild-type mice, T cells trafficked to the site of infection in neurons. Beside its role in maturation of antibody responses, our experiments suggest a novel function of CD40-CD40L interactions: to facilitate T-cell migration across the blood-brain barrier to control WNV infection.

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Section: Discussionsupporting

confidence: 83%

CD40-CD40 Ligand Interactions Promote Trafficking of CD8 ⁺ T Cells into the Brain and Protection against West Nile Virus Encephalitis

Sitati¹,

McCandless

Klein

et al. 2007

J Virol

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“…Clinical trials of early phases have shown that this approach is safe and provides clinical efficacy in addition to immune responses 16 17. Our group has recently described stimulating monoclonal antibodies against CD40 as an effective treatment against liver cancer in a rat model 12. The data suggest that the observed effects are due to activation of CD8 + , CD4 + and NK cells, the stimulation of leukocyte adhesion to tumour vessels and finally their migration into the tumour.…”

Section: Discussionmentioning

confidence: 99%

Transfection with CD40L induces tumour suppression by dendritic cell activation in an orthotopic mouse model of pancreatic adenocarcinoma

Serba

Schmidt

Wentzensen

et al. 2008

Gut

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“…Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, accounting for 85% to 90% of primary liver cancers 1, 2. The standard HCC treatments include surgical resection, liver transplantation, immunotherapy, radiotherapy and chemotherapy 3, 4. However, none of these treatments is very effective, and a large proportion of HCC patients have a poor prognosis because of rapid metastasis 4, 5.…”

Section: Introductionmentioning

confidence: 99%

Combined Aberrant Expression of NDRG2 and LDHA Predicts Hepatocellular Carcinoma Prognosis and Mediates the Anti-tumor Effect of Gemcitabine

Guo¹,

Li²,

Sun³

et al. 2019

Int. J. Biol. Sci.

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The Warburg effect is one of the important hallmarks of cancer. The activation of oncogene and inactivation of tumor suppressor gene contribute to the enhancement of glycolytic enzymes and the Warburg effect. The N-myc downstream regulated gene 2 (NDRG2) is a tumor suppressor gene and is frequently lost in various types of cancer. However, little is known about glycolytic function and therapeutic value of NDRG2 in hepatocellular carcinoma (HCC). In this study, we found that NDRG2 and lactate dehydrogenase A (LDHA) were aberrantly expressed in HCC and were closely related to the Warburg effect. The correlation between NDRG2 and LDHA expression predicted HCC prognosis and the clinical response to chemotherapy. NDRG2 expression was significantly decreased while LDHA expression was increased in HCC specimens. NDRG2 and LDHA expression was significantly correlated with differentiation status, vascular invasion, and TNM stage of HCC. NDRG2 inhibited LDHA expression, the Warburg effect and the growth of HCC cells. Furthermore, NDRG2 mediated gemcitabine-induced inhibition of LDHA expression and the Warburg effect in HCC cells. Taken together, our data suggest that NDRG2 plays an important role in inhibiting the Warburg effect and the malignant growth of HCC via LDHA. NDRG2 combined with LDHA might be powerful prognostic biomarkers and targets for chemotherapy treatment of HCC.

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Activating anti-CD40 antibodies induce tumour invasion by cytotoxic T-lymphocytes and inhibition of tumour growth in experimental liver cancer

Cited by 11 publications

References 24 publications

CD40-CD40 Ligand Interactions Promote Trafficking of CD8 ⁺ T Cells into the Brain and Protection against West Nile Virus Encephalitis

CD40-CD40 Ligand Interactions Promote Trafficking of CD8 ⁺ T Cells into the Brain and Protection against West Nile Virus Encephalitis

Transfection with CD40L induces tumour suppression by dendritic cell activation in an orthotopic mouse model of pancreatic adenocarcinoma

Combined Aberrant Expression of NDRG2 and LDHA Predicts Hepatocellular Carcinoma Prognosis and Mediates the Anti-tumor Effect of Gemcitabine

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Activating anti-CD40 antibodies induce tumour invasion by cytotoxic T-lymphocytes and inhibition of tumour growth in experimental liver cancer

Cited by 11 publications

References 24 publications

CD40-CD40 Ligand Interactions Promote Trafficking of CD8 + T Cells into the Brain and Protection against West Nile Virus Encephalitis

CD40-CD40 Ligand Interactions Promote Trafficking of CD8 + T Cells into the Brain and Protection against West Nile Virus Encephalitis

Transfection with CD40L induces tumour suppression by dendritic cell activation in an orthotopic mouse model of pancreatic adenocarcinoma

Combined Aberrant Expression of NDRG2 and LDHA Predicts Hepatocellular Carcinoma Prognosis and Mediates the Anti-tumor Effect of Gemcitabine

Contact Info

Product

Resources

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CD40-CD40 Ligand Interactions Promote Trafficking of CD8 ⁺ T Cells into the Brain and Protection against West Nile Virus Encephalitis

CD40-CD40 Ligand Interactions Promote Trafficking of CD8 ⁺ T Cells into the Brain and Protection against West Nile Virus Encephalitis