ArticleCellular immunology2023
SMAC mimetics inhibit human T cell proliferation and fail to augment type 1 cytokine responses.
Article in Cellular immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Xevinapant plus Chemoradiotherapy Negatively Sculpts the Tumor-Immune Microenvironment in Head and Neck Cancer.Cancer research communications · 2025Article
- Necroptosis-driven T cell activation promotes IL-6-mediated PD-L1 upregulation in cholangiocarcinoma cells: IL-6 gene signature as a biomarker for chemo-immunotherapy response.Biology direct · 2025Article
- Tazarotene-Induced Gene 3 (TIG3) Induces Apoptosis in Melanoma Cells Through the Modulation of Inhibitors of Apoptosis Proteins.Biomedicines · 2025Article
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4 authors at 1 institution in 1 country.
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Abstract
Second mitochondria-derived activator of caspases (SMAC) mimetics are small molecule drugs that mimic the activity of the endogenous SMAC protein. SMAC and SMAC mimetics antagonize inhibitors of apoptosis proteins (IAPs), thereby sensitizing cells to apoptosis. As such, SMAC mimetics are being tested in numerous clinical trials for cancer. In addition to their direct anti-cancer effect, it has been suggested that SMAC mimetics may activate T cells, thereby promoting anti-tumor immunity. Here, we tested the effect of three clinically relevant SMAC mimetics on activation of primary human T cells. As previously reported, SMAC mimetics killed tumor cells and activated non-canonical NF-κB in T cells at clinically relevant doses. Surprisingly, none of the SMAC mimetics augmented T cell responses. Rather, SMAC mimetics impaired T cell proliferation and decreased the proportion of IFNγ/TNFα double-producing T cells. These results question the assumption that SMAC mimetics are likely to boost anti-tumor immunity in cancer patients.
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