Blockade of Tumor Necrosis Factor α Signaling in Tumor-Associated Macrophages as a Radiosensitizing Strategy

Yu, Meng; Beckett, Michael A.; Liang, Hua; Mauceri, Helena J.; Rooijen, Nico van; Cohen, Kenneth S.; Weichselbaum, Ralph R.

doi:10.1158/0008-5472.can-09-2995

Cited by 169 publications

(155 citation statements)

References 47 publications

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“…This is mediated by a release of various cytokines, superoxide, and nitric oxide (8). All of which are capable of causing tissue damage (22) by signaling through pro-apoptosis mediator TNF-␣, Fas ligand, nitric oxide, and superoxide (23,24).…”

Section: Radiation-induced Bystander Responses (Rbr)mentioning

confidence: 99%

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TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Nontargeted Effects in Bone Marrow-derived Endothelial Progenitor Cells

Sasi¹,

Song²,

Park³

et al. 2014

Journal of Biological Chemistry

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Background: Ionizing radiation can induce DNA damage in nonirradiated (N-IR) cells via nontargeted effects (NTE). Results: TNF-␣ and IL-1␣ mediate NTE in N-IR bone marrow-derived EPCs, and neutralizing TNF-␣ diminishes NTE in WT and p55 knock-out BM-EPCs. Conclusion: TNF-TNFR2/p75 signaling alters accumulation of inflammatory cytokines that attenuate NTE in N-IR EPCs. Significance: TNFR2/p75 may represent a gene target for mitigation of delayed RBR in BM-EPCs.

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Section: Radiation-induced Bystander Responses (Rbr)mentioning

confidence: 99%

“…TNF-␣ is a pro-inflammatory cytokine whose expression is known to be highly up-regulated in many tissues and cells after IR (23,25). TNF-␣ is a 17-kDa polypeptide that specifically binds and exerts its function via two cell surface receptors, TNFR1 (p55) and TNFR2 (p75).…”

Section: Radiation-induced Bystander Responses (Rbr)mentioning

confidence: 99%

TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Nontargeted Effects in Bone Marrow-derived Endothelial Progenitor Cells

Sasi¹,

Song²,

Park³

et al. 2014

Journal of Biological Chemistry

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“…19 In vivo , it is rather difficult to assess the direct effect of IR on macrophage activation. However, recent studies in the tumor stroma showed that high doses of IR (> 8Gy) promote anti-inflammatory activation of macrophages, 20 and low doses (< 2Gy) combined with immunotherapy induce proinflammatory activation of macrophages that favor tumor elimination. 21 These data suggest that there is a direct effect of IR on macrophage activation.…”

Section: Macrophage Response To Radiotherapymentioning

confidence: 99%

Macrophages in radiation injury: a new therapeutic target

2018

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“…On the other hand, ionizing radiation can also generate chemotactic signals that recruit several myeloid-cell types with distinct roles in T cell suppression (114)(115)(116).…”

Section: Multimodality Treatments and Future Directionsmentioning

confidence: 99%

New Drug Combination Strategies in Melanoma: Current Status and Future DirectionsNew Drug Combination Strategies in Melanoma: Current Status and Future Directions

Najem

Krayem

Perdrix

et al. 2017

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Abstract. Melanoma is the deadliest form of skinIncidence and mortality rates for melanomas, the most common form of cancer in people aged from 25 to 29, continue to rise faster than any other cancer type. Although melanoma accounts for only a small percentage of skin cancers, it is responsible for the majority of deaths of all skin cancers (1, 2). Increased understanding of the molecular events involved in melanoma development has led to the identification of novel targets and to the development of new targeted agents. Gene alterations identified in melanoma pointed to distinct molecular subsets of tumors with direct implications in therapeutic strategies. Among these, activating BRAF mutations occur in 50-60% of melanomas (V600E substitution represents about 90% of BRAF mutations), NRAS mutations in 20-30% of melanomas (mutually exclusive with BRAF mutation), KIT mutations and/or amplification in 39% of mucosal and 36% of acral melanomas (3, 4). These mutations opened new therapeutic perspectives targeting the MAPK pathway (hyperactivated in 90% of melanomas) with V600E BRAF, MEK or RTK inhibitors (5-7).Vemurafenib and dabrafenib, specific inhibitors of the mutant BRAF (V600E), have been approved by the Food and Drug Administration (FDA) in 2011 and 2013 respectively, for the treatment of patients with unresectable or metastatic melanoma carrying the V600E mutation in BRAF. Furthermore, trametinib a selective inhibitor of MEK1/2 was approved for the same indication in 2013. The approval of these inhibitors was based on improved rates of overall and progression-free survival compared to chemotherapy in phase III clinical trials (6, 8, 9). Moreover, among new MEK inhibitors in clinical development, pimasertib and binimetinib (MEK162) have been recently reported to be particularly promising in the case of patients with mutant NRAS melanoma (10-12). Finally, the results of clinical trials evaluating RTK inhibitors sunitinib and imatinib in patients presenting mutated c-KIT have been published and showed an average response rate of 20% (7, 13).Targeting MAPK pathway in melanoma with MAPK inhibitors has shown clinical benefit. However, the short duration of response and progression-free survival in patients due to resistance or to general toxicity indicate that 5941

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Blockade of Tumor Necrosis Factor α Signaling in Tumor-Associated Macrophages as a Radiosensitizing Strategy

Abstract: Most cancer patients receive radiotherapy during the course of their disease.

Cited by 169 publications

References 47 publications

TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Nontargeted Effects in Bone Marrow-derived Endothelial Progenitor Cells

TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Nontargeted Effects in Bone Marrow-derived Endothelial Progenitor Cells

Macrophages in radiation injury: a new therapeutic target

New Drug Combination Strategies in Melanoma: Current Status and Future DirectionsNew Drug Combination Strategies in Melanoma: Current Status and Future Directions

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