ArticleJCI insight2020
PPT1 inhibition enhances the antitumor activity of anti-PD-1 antibody in melanoma.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 62 papers, 1 of them a synthesis that pooled it.
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
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Pooled it
- SMAD4 loss is associated with response to neoadjuvant chemotherapy plus hydroxychloroquine in patients with pancreatic adenocarcinoma.Clinical and translational science · 2021Trial
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Dietary sulfur amino acids enhance anti-tumor immunity in colon cancer via an NKT cell-XCL1-cDC1 circuit.Immunity · 2026Article
- The functional roles and therapeutic potential of protein palmitoylation in hepatocellular carcinoma.Discover oncology · 2026Review
- TLR7 induces autophagy in non-small cell lung cancer tumor cells and influences anti-tumors responses in patients.Translational lung cancer research · 2026Article
- Targeting Autophagy to Overcome Chemoresistance and Immune Resistance in Triple-Negative Breast Cancer.Cancers · 2026Review
- Autophagy Modulates Immunogenic Cell Death in Cancer.Cancers · 2026Review
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- Palmitoylation modulates antitumor immunity.Molecular biology reports · 2025Review
- PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Autophagy inhibition improves the efficacy of anlotinib and PD-1 inhibitors in the treatment of NSCLC.Journal for immunotherapy of cancer · 2025Article
- Palmitic acid and palmitoylation in cancer: Understanding, insights, and challenges.Innovation (Cambridge (Mass.)) · 2025Review
- Review
- Review
- Palmitoylation in cancer: decoding its roles in signal transduction, tumor immunity, and emerging therapeutic opportunities.Frontiers in immunology · 2025Review
- Advances in targeting protein S-palmitoylation in tumor immunity and therapy.Frontiers in oncology · 2025Review
- Key immune cells and their crosstalk in the tumor microenvironment of bladder cancer: insights for innovative therapies.Exploration of targeted anti-tumor therapy · 2025Review
- cGAS/STING in skin melanoma: from molecular mechanisms to therapeutics.Cell communication and signaling : CCS · 2024Review
- Investigating PPT2's role in ovarian cancer prognosis and immunotherapy outcomes.Journal of ovarian research · 2024Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
New strategies are needed to enhance the efficacy of anti-programmed cell death protein antibody (anti-PD-1 Ab) in cancer. Here, we report that inhibiting palmitoyl-protein thioesterase 1 (PPT1), a target of chloroquine derivatives like hydroxychloroquine (HCQ), enhances the antitumor efficacy of anti-PD-1 Ab in melanoma. The combination resulted in tumor growth impairment and improved survival in mouse models. Genetic suppression of core autophagy genes, but not Ppt1, in cancer cells reduced priming and cytotoxic capacity of primed T cells. Exposure of antigen-primed T cells to macrophage-conditioned medium derived from macrophages treated with PPT1 inhibitors enhanced melanoma-specific killing. Genetic or chemical Ppt1 inhibition resulted in M2 to M1 phenotype switching in macrophages. The combination was associated with a reduction in myeloid-derived suppressor cells in the tumor. Ppt1 inhibition by HCQ, or DC661, induced cyclic GMP-AMP synthase/stimulator of interferon genes/TANK binding kinase 1 pathway activation and the secretion of interferon-β in macrophages, the latter being a key component for augmented T cell-mediated cytotoxicity. Genetic Ppt1 inhibition produced similar findings. These data provide the rationale for this combination in melanoma clinical trials and further investigation in other cancers.
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.