ArticleCell death & disease2015
Modulation of radiochemoimmunotherapy-induced B16 melanoma cell death by the pan-caspase inhibitor zVAD-fmk induces anti-tumor immunity in a HMGB1-, nucleotide- and T-cell-dependent manner.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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63 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Interaction of HIF-1a with various cell death pathways in tumor immune microenvironment (TIME).Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Innovative research on predicting skin flaps necrosis through quantification of the USP4/TNFAIP2 regulated 'M1 macrophages-Tregs axis' via skin barrier monitoring technology.Burns & trauma · 2026Article
- Cracking the code of cancer immunotherapy resistance: emerging roles of pyroptosis and necroptosis.Journal of experimental & clinical cancer research : CR · 2025Review
- RPA1 protects DNA damage-induced PANoptosis in limb development.Science advances · 2025Article
- The role of non-coding RNAs in the regulation of cell death pathways in melanoma.Discover oncology · 2025Review
- Review
- Targeting regulated cell death: Apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis in anticancer immunity.Journal of translational internal medicine · 2025Article
- Targeting ferroptosis, pyroptosis and necroptosis for cancer immunotherapy in melanoma: mechanistic insights and clinical perspectives.Frontiers in immunology · 2025Review
- PANoptosis: bridging apoptosis, pyroptosis, and necroptosis in cancer progression and treatment.Cancer gene therapy · 2024Review
- Characteristics and significance of programmed cell death-related gene expression signature in skin cutaneous melanoma.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2024Article
- Emerging role of immunogenic cell death in cancer immunotherapy.Frontiers in immunology · 2024Review
- Review
- Carbonic anhydrase IX inhibitor S4 triggers release of DAMPs related to immunogenic cell death in glioma cells via endoplasmic reticulum stress pathway.Cell communication and signaling : CCS · 2023Article
- Harnessing the Potential of Non-Apoptotic Cell Death Processes in the Treatment of Drug-Resistant Melanoma.International journal of molecular sciences · 2023Review
- Immunogenic hypofractionated radiotherapy sensitising head and neck squamous cell carcinoma to anti-PD-L1 therapy in MDSC-dependent manner.British journal of cancer · 2023Article
- Immunogenic cell death in cancer immunotherapy.BMB reports · 2023Review
- Immunogenic cell death after combined treatment with radiation and ATR inhibitors is dually regulated by apoptotic caspases.Frontiers in immunology · 2023Article
- CD300b regulates intestinal inflammation and promotes repair in colitis.Frontiers in immunology · 2023Article
- Article
- Necroptosis: A Pathogenic Negotiator in Human Diseases.International journal of molecular sciences · 2022Review
3 more citing papers are in PubMed but not listed here.
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5 authors at 2 institutions in 1 country.
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Abstract
One prerequisite that radiotherapy (RT) and chemotherapy (CT) result in anti-tumor immune responses is triggering of immunogenic cell death forms such as necroptosis. The latter is inducible by inhibition of apoptosis with the pan-caspase inhibitor zVAD-fmk. The design of multimodal therapies that overcome melanoma's resistance to apoptosis is a big challenge of oncoimmunology. As hints exist that immune stimulation by hyperthermia (HT) augments the efficacy of melanoma therapies and that tumors can be sensitized for RT with zVAD-fmk, we asked whether combinations of RT with dacarbazine (DTIC) and/or HT induce immunogenic melanoma cell death and how this is especially influenced by zVAD-fmk. Necroptosis was inducible in poorly immunogenic B16-F10 melanoma cells and zVAD-fmk generally increased melanoma cell necrosis concomitantly with the release of HMGB1. Supernatants (SNs) of melanoma cells whose cell death was modulated with zVAD-fmk induced an upregulation of the activation markers CD86 and MHCII on macrophages. The same was seen on dendritic cells (DCs), but only when zVAD-fmk was added to multimodal tumor treatments including DTIC. DCs of MyD88 KO mice and DCs incubated with SNs containing apyrase did not increase the expression of these activation markers on their surface. The in vivo experiments revealed that zVAD-fmk decreases the tumor growth significantly and results in a significantly reduced tumor infiltration of Tregs when added to multimodal treatment of the tumor with RT, DTIC and HT. Further, a significantly increased DC and CD8+ T-cell infiltration into the tumor and in the draining lymph nodes was induced, as well as an increased expression of IFNγ by CD8+ T cells. However, zVAD-fmk did not further reduce tumor growth in MyD88 KO mice, mice treated with apyrase or RAG KO mice. We conclude that HMGB1, nucleotides and CD8+ T cells mediate zVAD-fmk induced anti-melanoma immune reactions in multimodal therapy settings.
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