An endotoxin-induced serum factor that causes necrosis of tumors.

Carswell, Elizabeth A.; Old, Lloyd J.; Kassel, Robert; Green, S; Fiore, Nancy; Williamson, Barbara

doi:10.1073/pnas.72.9.3666

Cited by 3,830 publications

(1,913 citation statements)

References 8 publications

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“…53 , 54 TNFα mediates an anti-tumor effect both by inhibiting angiogenesis and by directly inducing cancer cell death. 55 , 56 Likewise, IFNγ has also been suggested to prevent tumor angiogenesis. In a rat glioma model, retroviral delivery of IFNγ was further shown to improve survival.…”

Section: Discussionmentioning

confidence: 99%

TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM

et al. 2018

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The use of inhibitory checkpoint blockade in the management of glioblastoma has been studied in both preclinical and clinical settings. TIGIT is a novel checkpoint inhibitor recently discovered to play a role in cancer immunity. In this study, we sought to determine the effect of anti-PD-1 and anti-TIGIT combination therapy on survival in a murine glioblastoma (GBM) model, and to elucidate the underlying immune mechanisms. Using mice with intracranial GL261-luc+ tumors, we found that TIGIT expression was upregulated on CD8+ and regulatory T cells (Tregs) in the brain compared to draining cervical lymph nodes (CLN) and spleen. We then demonstrated that treatment using anti-PD-1 and anti-TIGIT dual therapy significantly improved survival compared to control and monotherapy groups. The therapeutic effect was correlated with both increased effector T cell function and downregulation of suppressive Tregs and tumor-infiltrating dendritic cells (TIDCs). Clinically, TIGIT expression on tumor-infiltrating lymphocytes was shown to be elevated in patient GBM samples, suggesting that the TIGIT pathway may be a valuable therapeutic target. Expression of the TIGIT ligand, PVR, further portended a poor survival outcome in patients with low-grade glioma. We conclude that anti-TIGIT is an effective treatment strategy against murine GBM when used in combination with anti-PD-1, improving overall survival via modifications of both the T cell and myeloid compartments. Given evidence of PVR expression on human GBM cells, TIGIT presents as a promising immune therapeutic target in the management of these patients.

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Section: Discussionmentioning

confidence: 99%

TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM

et al. 2018

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“…11 Its proinflammatory and antitumor activity was first noticed more than 100 y ago, but the protein was only identified in 1975. 12 Its gene was cloned in 1984, 13 and it was mapped to the short arm of chromosome 6, 14 near the HLA-B focus in the MHC. TNF-a is mainly produced by the activated macrophages and monocytes, although DC, mast cells, neutrophils, keratinocytes, smooth muscle cells, intestinal paneth cells, tumor cells, and microglial cells might also produce and release TNF-a.…”

Section: Introductionmentioning

confidence: 99%

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

Pirtskhalaishvili

Shurin

Esche

et al. 2001

Prostate Cancer Prostatic Dis

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We have recently shown that human prostate cancer (PCa) cells induced apoptotic death of the most potent antigen-presenting cells, dendritic cells (DC), which are responsible for the induction of specific antitumor immune responses. Here we have evaluated the effect of murine PCa cells RM-1 on the survival of immature and tumor necrosis factor-a (TNF-a)-stimulated mature DC. PCa cells and DC were co-incubated for 24 -48 h and DC apoptosis was assessed by morphologic criteria, Annexin V assay, and TUNEL staining. We have shown that co-incubation of RM-1 cells with DC is accompanied by an increased level of DC apoptosis, which was mediated by decreased expression of anti-apoptotic protein Bcl-2. Stimulation of DC maturation by TNF-a resulted in increased resistance of DC to PCa-induced apoptosis. In TNF-a treated mature DC, but not in immature DC, the expression of Bcl-2 was not blocked after exposure to RM-1-derived factors. Thus, these data suggest that TNF-a-induced maturation of DC increases their resistance to PCa induced apoptosis. This is likely to be due to the stabilizing of the expression of anti-apoptotic protein Bcl-2. The difference in the sensitivity of mature and immature DC to PCa-induced cell death should be considered during the design of DC-based clinical trials for PCa patients. Prostate Cancer and Prostatic Diseases (2001) 4, 221-227.

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“…It was initially described to induce hemorrhagic necrosis in transplanted tumors [27]. TNFα effects are principally mediated through two distinct receptors TNFα receptor (TNFR) I and II.…”

Section: Tumor Necrosis Factor Alphamentioning

confidence: 99%

Linking anemia to inflammation and cancer: The crucial role of TNFα

Buck

Morceau

Grigorakaki

et al. 2009

Biochemical Pharmacology

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Erythropoiesis is considered as a multistep and tightly regulated process under the control of a series of cytokines including erythropoietin (Epo). Epo activates specific signaling pathways and leads to activation of key transcription factors such as GATA-1, in order to ensure erythroid differentiation. Deregulation leads to a decreased number of red blood cells, a hemoglobin deficiency, thus a limited oxygen-carrying capacity in the blood. Anemia represents a frequent complication in various diseases such as cancer or inflammatory diseases. It reduces both quality of life and prognosis in patients. Tumor necrosis factor alpha (TNFα) was described to be involved in the pathogenesis of inflammation and cancer related anemia. Blood transfusions and erythroid stimulating agents (ESAs) including human recombinant Epo (rhuEpo) are currently used as efficient treatments. Moreover, the recently described conflicting effects of ESAs in distinct studies require further investigations on the molecular mechanisms involved in TNFα-caused anemia. The present study aims to evaluate the current knowledge and the importance of the effect of the proinflammatory cytokine TNFα on erythropoiesis in inflammatory and malignant conditions.

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An endotoxin-induced serum factor that causes necrosis of tumors.

Cited by 3,830 publications

References 8 publications

TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM

TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

Linking anemia to inflammation and cancer: The crucial role of TNFα

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