ArticleJournal for immunotherapy of cancer2023
Androgen receptor blockade resistance with enzalutamide in prostate cancer results in immunosuppressive alterations in the tumor immune microenvironment.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Clinical Benefit and Safety of Combined Immunotherapy and Targeted Therapy in Prostate Cancer.International journal of cancer · 2026Pooled it
- Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Tumor‑immune spatiotemporal co‑evolution: A new paradigm for understanding and overcoming therapy resistance in metastatic castration‑resistant prostate cancer (Review).International journal of molecular medicine · 2026Review
- Androgen receptor drives lenvatinib resistance in hepatocellular carcinoma through transcriptional activation of EIF3I and a downstream ceRNA axis.Oncology letters · 2026Article
- Glutamate Ionotropic Kainate Receptors as Therapeutic Targets in Enzalutamide-Resistant and Neuroendocrine Prostate Cancer.International journal of molecular sciences · 2026Article
- Heterogeneity of urinary system tumors: novel avenues for targeted therapy and precision medicine.Journal of advanced research · 2026Review
- ANXA2-mediated Phagocytosis Generates ARAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PARP inhibitors restore NK cell function via secretory crosstalk with tumor cells in prostate cancer.The Journal of clinical investigation · 2026Article
- Cancer Cell-Intrinsic Cholesterol Induces Lipid-Associated Macrophage Differentiation via SP1 Palmitoylation to Promote Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Androgens are a Key Factor Affecting Immune Related Diseases.The world journal of men's health · 2026Review
- A Deep Learning-Based Multimodal Clinico-Histology-Genomic Prognostic Model in Prostate Cancer.Annals of surgical oncology · 2026Article
- The Multifaceted Role of Androgen Receptor Signaling in Immunity: Implications for Oncology.Molecular cancer research : MCR · 2026Review
- Tumor immune microenvironment facilitates resistance to KRAS G12C inhibitor sotorasib by altered PD-L1 expression.Journal for immunotherapy of cancer · 2026Article
- Targeting NXPH4/ALDH1L2 signaling suppresses enzalutamide resistance in prostate cancer.Cell death discovery · 2026Article
- Machine learning-based identification of hub genes and prognostic biomarkers in prostate cancer.Frontiers in genetics · 2026Article
- Immune-tumor cell ligand-receptor axes driving metabolic reprogramming and therapeutic resistance in cancer.Frontiers in immunology · 2026Review
- Integrative Transcriptomic Analysis and Preliminary Peripheral Blood Evaluation IdentifyInternational journal of general medicine · 2026Article
- Molecular innate immune programs of tumor-associated macrophages in immune checkpoint blockade resistance: a staged framework from suppressive circuitry to translational bottlenecks.Frontiers in immunology · 2026Review
- Targeted protein degradation dismantles undruggable targets to reverse immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
- Targeting CAMK1D-engineered nanoactivator suppresses cancer stem cell maintenance and immune evasion in enzalutamide-resistant prostate cancer.Theranostics · 2026Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEmerging data suggest that patients with enzalutamide-treated prostate cancer with increased programmed death-ligand 1 (PD-L1) expression may benefit from anti-PD-L1 treatment. Unfortunately, the Phase III IMbassador250 clinical trial revealed that the combination of atezolizumab (a PD-L1 inhibitor) and enzalutamide failed to extend overall survival in patients with castration-resistant prostate cancer (CRPC). However, the mechanisms underlying treatment failure remain unknown.
methodsHuman CRPC C4-2B cells and murine Myc-CaP cells were chronically exposed to increasing concentrations of enzalutamide and the cells resistant to enzalutamide were referred to as C4-2B MDVR and Myc-CaP MDVR, respectively. The mechanisms of action in drug-resistant prostate cancer cells were determined using RNA sequencing analyses, RNA interference, real-time PCR, western blotting, and co-culturing technologies. Myc-CaP and Myc-CaP MDVR tumors were established in syngeneic FVB mice, and tumor-infiltrating leukocytes were isolated after enzalutamide treatment. The stained immune cells were determined by flow cytometry, and the data were analyzed using FlowJo.
resultsImmune-related signaling pathways (interferon alpha/gamma response, inflammatory response, and cell chemotaxis) were suppressed in human enzalutamide-resistant prostate cancer cells. PD-L1 was overexpressed and negatively regulated by androgen receptor signaling in resistant cells and patient with CRPC cohorts. Enzalutamide treatment decreased CD8
conclusionsOur study suggests that immunosuppressive signaling can be promoted directly by enzalutamide-resistant prostate cancer cells and may be a potential means by which the efficacy of immune checkpoint inhibitors in enzalutamide-resistant prostate cancer is diminished.
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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.