ArticleCancer immunology research2022
Targeting WEE1/AKT Restores p53-Dependent Natural Killer-Cell Activation to Induce Immune Checkpoint Blockade Responses in "Cold" Melanoma.
Article in Cancer immunology research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Protein kinase WEE1 promotes cardiomyocytes ferroptosis and cardiac hypertrophy via the NF-κB/LCN2 axis.Acta pharmacologica Sinica · 2026Article
- Unraveling the Molecular Mechanisms Linking Cigarette Smoke Exposure to Skin Damage.International journal of molecular sciences · 2026Article
- Therapeutic targeting of cell death-immune crosstalk in cancer to rewire the tumor immune microenvironment.Molecular cancer · 2025Review
- The impact of zinc and testosterone co-treatment on tumourigenesis in prostate cancer: a novel model.BMC cancer · 2025Article
- Adjusting the scope of natural killer cells in cancer therapy.Cellular & molecular immunology · 2025Review
- Rescuing natural killer cells from the cancer wilderness.Journal for immunotherapy of cancer · 2025Article
- ULBP2 Promotes Tumor Progression by Suppressing NKG2D-Mediated Anti-Tumor Immunity.International journal of molecular sciences · 2025Article
- Inverse correlation between TP53 gene status and PD-L1 protein levels in a melanoma cell model depends on an IRF1/SOX10 regulatory axis.Cellular & molecular biology letters · 2024Article
- Crosstalk among WEE1 Kinase, AKT, and GSK3 in Nav1.2 Channelosome Regulation.International journal of molecular sciences · 2024Article
- p53 at the crossroads of tumor immunity.Nature cancer · 2024Review
- Master regulator: p53's pivotal role in steering NK-cell tumor patrol.Frontiers in immunology · 2024Review
- NK cell-based tumor immunotherapy.Bioactive materials · 2024Review
- Identification of DNA methylation-regulated WEE1 with potential implications in prognosis and immunotherapy for low-grade glioma.Cancer biomarkers : section A of Disease markers · 2024Article
- The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer.Frontiers in cell and developmental biology · 2023Review
- An Immunogenic Cell Death-Related Gene Signature Reflects Immune Landscape and Predicts Prognosis in Melanoma Independently of BRAF V600E Status.BioMed research international · 2023Article
- Upregulated miR-322-5p regulates cell cycle and promotes cell proliferation and apoptosis by directly targeting Wee1 in mice liver injury.Cell cycle (Georgetown, Tex.) · 2022Article
- Chimeric Oncolytic Adenovirus Armed Chemokine Rantes for Treatment of Breast Cancer.Bioengineering (Basel, Switzerland) · 2022Article
- Significance of immunogenic cell death-related genes in prognosis prediction and immune microenvironment landscape of patients with cutaneous melanoma.Frontiers in genetics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Immunotherapy has revolutionized cancer treatment. Unfortunately, most tumor types do not respond to immunotherapy due to a lack of immune infiltration or "cold" tumor microenvironment (TME), a contributing factor in treatment failure. Activation of the p53 pathway can increase apoptosis of cancer cells, leading to enhanced antigen presentation, and can stimulate natural killer (NK) cells through expression of stress ligands. Therefore, modulation of the p53 pathway in cancer cells with wild-type TP53 has the potential to enhance tumor immunogenicity to NK cells, produce an inflammatory TME, and ultimately lead to tumor regression. In this study, we report simultaneous targeting of the AKT/WEE1 pathways is a novel and tolerable approach to synergistically induce p53 activation to inhibit tumor development. This approach reduced the growth of melanoma cells and induced plasma membrane surface localization of the ER-resident protein calreticulin, an indicator of immunogenic cell death (ICD). Increase in ICD led to enhanced expression of stress ligands recognized by the activating NK-cell receptor NKG2D, promoting tumor lysis. WEE1/AKT inhibition resulted in recruitment and activation of immune cells, including NK cells, in the TME, triggering an inflammatory cascade that transformed the "cold" TME of B16F10 melanoma into a "hot" TME that responded to anti-programmed cell death protein 1 (anti-PD-1), resulting in complete regression of established tumors. These results suggest that AKT/WEE1 pathway inhibition is a potential approach to broaden the utility of class-leading anti-PD-1 therapies by enhancing p53-mediated, NK cell-dependent tumor inflammation and supports the translation of this novel approach to further improve response rates for metastatic melanoma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.