The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization
Open accessAbstract
Summary Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a‐&bgr;‐catenin‐peroxisome proliferator‐activated receptor‐&ggr; (PPAR‐&ggr;) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase‐1A (CPT1A) fatty acid transporter. This FAO shift increased the protoporphyrin IX prosthetic group of indoleamine 2,3‐dioxgenase‐1 (IDO) while suppressing interleukin(IL)‐6 and IL‐12 cytokine expression, culminating in enhanced IDO activity and the generation of regulatory T cells. We demonstrated that blockade of this pathway augmented anti‐melanoma immunity, enhanced the activity of anti‐PD‐1 antibody immunotherapy, and suppressed disease progression in a transgenic melanoma model. This work implicates a role for tumor‐mediated metabolic reprogramming of local DCs in immune evasion and immunotherapy resistance. Graphical Abstract Figure. No Caption available. HighlightsMelanomas metabolically reprogram local DCs to induce immune toleranceMelanoma‐derived Wnt5a triggers DC FAO via a &bgr;‐catenin‐PPAR‐&ggr; pathwayDC FAO drives IDO enzymatic activity by promoting protoporphyrin IX synthesisInhibiting the Wnt5a‐&bgr;‐catenin‐CPT1A pathway enhances anti‐PD‐1 antibody activity &NA; Previous studies suggest that DC tolerization plays a role in tumor‐mediated immune evasion. The mechanism by which cancers promote this process remains poorly understood. Zhao et al. demonstrate that melanomas generate a site of immune privilege by driving DC fatty acid oxidation via a Wnt5a‐&bgr;‐catenin‐PPAR‐&ggr; signaling pathway that culminates in the induction of IDO enzyme activity. Inhibiting this pathway reverses DC tolerization and enhances anti‐PD‐1 antibody efficacy in a transgenic model of melanoma.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma
Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., Berent-Maoz, B., Pang, J., Chmielowski, B., Cherry, G., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.065 · Cited by 3,448
Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity
Spranger, S., Bao, R., & Gajewski, T. F. (2015) · Nature · doi:10.1038/nature14404 · Cited by 2,830
Spranger, S., Spaapen, R. M., Zha, Y., Williams, J., Meng, Y., Ha, T. T., & Gajewski, T. F. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006504 · Cited by 1,677
Spranger, S., Dai, D., Horton, B., & Gajewski, T. F. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.04.003 · Cited by 1,441
Everts, B., Amiel, E., Huang, S. C.-C., Smith, A. M., Chang, C.-H., Lam, W. Y., Redmann, V., Freitas, T. C., Blagih, J., van der Windt, G. J. W., et al. (2014) · Nature Immunology · doi:10.1038/ni.2833 · Cited by 1,064
Munn, D. H., Sharma, M. D., Hou, D., Baban, B., Lee, J. R., Antonia, S. J., Messina, J. L., Chandler, P., Koni, P. A., & Mellor, A. L. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21583 · Cited by 852
Indoleamine 2,3-dioxygenase. Purification and some properties
Shimizu, T., Nomiyama, S., Hirata, F., & Hayaishi, O. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30447-7 · Cited by 367 · cited 1×
“IDO requires the heme prosthetic group, protoporphyrin IX (PpIX), for full enzymatic activity (Shimizu et al., 1978).”
Cited by
Lipid metabolism in cancer: New perspectives and emerging mechanisms
Broadfield, L. A., Pane, A. A., Talebi, A., Swinnen, J. V., & Fendt, S.-M. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.04.013 · Cited by 758
Fatty acid oxidation: An emerging facet of metabolic transformation in cancer
Ma, Y., Temkin, S. M., Hawkridge, A. M., Guo, C., Wang, W., Wang, X.-Y., & Fang, X. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.08.006 · Cited by 531
Phenotype plasticity as enabler of melanoma progression and therapy resistance
Arozarena, I., & Wellbrock, C. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0154-4 · Cited by 381
WNT/β-Catenin Signaling Pathway Regulating T Cell-Inflammation in the Tumor Microenvironment
Li, X., Xiang, Y., Li, F., Yin, C., Li, B., & Ke, X. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02293 · Cited by 291
Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances
Xue, C., Chu, Q., Shi, Q., Zeng, Y., Lu, J., & Li, L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02142-w · Cited by 281
Metadata
- Authors
- Zhao, F., Xiao, C., Evans, K. S., Theivanthiran, T., DeVito, N., Holtzhausen, A., Liu, J., Liu, X., Boczkowski, D., Nair, S., Locasale, J. W., & Hanks, B. A.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 48
- Issue
- 1
- Pages
- 147-160.e7
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2783680887
- Cited by
- 289
- References
- 7
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization. https://app.cochat.ai/papers/10.1016/j.immuni.2017.12.004
- The paper
- Zhao, F., Xiao, C., Evans, K. S., Theivanthiran, T., DeVito, N., Holtzhausen, A., Liu, J., Liu, X., Boczkowski, D., Nair, S., Locasale, J. W., & Hanks, B. A. (2018). Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization. Immunity. https://doi.org/10.1016/j.immuni.2017.12.004
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
