ArticleCancer immunology, immunotherapy : CII2025
The ATR inhibitor tuvusertib (M1774) sensitizes prostate carcinoma to natural killer cell-mediated cytotoxicity, which is further augmented by the IL-15 receptor superagonist N-803.
Article in Cancer immunology, immunotherapy : CII, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High levels of replication stress make cancer cells vulnerable to therapies targeting DNA damage response (DDR) proteins, such as ataxia telangiectasia and Rad3-related (ATR) protein kinase. ATR is a key mediator of the replication stress response and plays a vital role in maintaining genomic stability. This study investigates the immunomodulatory potential of the ATR inhibitor (ATRi) tuvusertib to improve the targeting of prostate cancer (PCa) by immunotherapy. Tuvusertib pretreatment sensitized human PCa cells (DU145 and 22Rv1) to PBMC-derived natural killer (NK)-mediated lysis. Flow cytometric analysis identified upregulation of death receptor tumor-necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), NKG2D ligand ULBP-1, and programmed death-ligand 1 (PD-L1) as a potential immunomodulatory effect of tuvusertib. Enhanced avelumab-mediated antibody-dependent cell-mediated cytotoxicity and lysis by PD-L1 targeting high-affinity NK (PD-L1 t-haNK) cells were observed in tuvusertib-treated DU145. Tuvusertib sensitized cells to lysis by recombinant human TRAIL, and TRAIL signaling blockade reduced NK-mediated lysis of tuvusertib-exposed cells. RNA analysis revealed elevated p21 and reduced Bcl-xL transcript levels in tuvusertib-treated DU145, suggesting an accumulation of DNA damage and suppression of anti-apoptotic signaling, respectively. Pretreatment of NK cells with the interleukin-15 (IL-15) receptor superagonist N-803 (nogapendekin alfa inbakicept) further enhaced the lysis of tuvusertib-exposed cells. In vivo in the DU145 PCa xenograft model, tuvusertib and N-803 combination therapy demonstrated marked and significant antitumor efficacy relative to either monotherapy, eliciting superior tumor growth control and prolonging survival. Our findings support further investigation into the use of ATRi with immune checkpoint blockade and/or immune-stimulating agents in prostate cancer.
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.