The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Tumor-Associated Macrophages Enhance Tumor Hypoxia and Aerobic Glycolysis
Abstract
Tumor hypoxia and aerobic glycolysis are well-known resistance factors for anticancer therapies. Here, we demonstrate that tumor-associated macrophages (TAM) enhance tumor hypoxia and aerobic glycolysis in mice subcutaneous tumors and in patients with non–small cell lung cancer (NSCLC). We found a strong correlation between CD68 TAM immunostaining and PET 18fluoro-deoxyglucose (FDG) uptake in 98 matched tumors of patients with NSCLC. We also observed a significant correlation between CD68 and glycolytic gene signatures in 513 patients with NSCLC from The Cancer Genome Atlas database. TAM secreted TNFα to promote tumor cell glycolysis, whereas increased AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1-alpha in TAM facilitated tumor hypoxia. Depletion of TAM by clodronate was sufficient to abrogate aerobic glycolysis and tumor hypoxia, thereby improving tumor response to anticancer therapies. TAM depletion led to a significant increase in programmed death-ligand 1 (PD-L1) expression in aerobic cancer cells as well as T-cell infiltration in tumors, resulting in antitumor efficacy by PD-L1 antibodies, which were otherwise completely ineffective. These data suggest that TAM can significantly alter tumor metabolism, further complicating tumor response to anticancer therapies, including immunotherapy. Significance: These findings show that tumor-associated macrophages can significantly modulate tumor metabolism, hindering the efficacy of anticancer therapies, including anti-PD-L1 immunotherapy.
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
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Tumor-Associated Macrophages: From Mechanisms to Therapy
Noy, R., & Pollard, J. W. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.010 · Cited by 4,089
Tumour-educated macrophages promote tumour progression and metastasis
Pollard, J. W. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1256 · Cited by 3,367
Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression
Chang, C.-H., Qiu, J., O’Sullivan, D., Buck, M. D., Noguchi, T., Curtis, J. D., Chen, Q., Gindin, M., Gubin, M. M., van der Windt, G. J. W., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.016 · Cited by 3,331
Exploiting tumour hypoxia in cancer treatment
Brown, J. M., & Wilson, W. R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1367 · Cited by 2,828
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491
Tumor cell metabolism: cancer's Achilles' heel
Kroemer, G., & Pouyssegur, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.005 · Cited by 2,337
PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity
Gordon, S. R., Maute, R. L., Dulken, B. W., Hutter, G., George, B. M., McCracken, M. N., Gupta, R., Tsai, J. M., Sinha, R., Corey, D., et al. (2017) · Nature · doi:10.1038/nature22396 · Cited by 2,247
Self-citationInterferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression
Garcia-Diaz, A., Shin, D. S., Moreno, B. H., Saco, J., Escuin-Ordinas, H., Rodriguez, G. A., Zaretsky, J. M., Sun, L., Hugo, W., Wang, X., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.031 · Cited by 1,942
Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice
Sonveaux, P., Végran, F., Schroeder, T., Wergin, M. C., Verrax, J., Rabbani, Z. N., De Saedeleer, C. J., Kennedy, K. M., Diepart, C., Jordan, B. F., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36843 · Cited by 1,624
Cited by
Macrophages and metabolism in the tumor microenvironment
Vitale, I., Manic, G., Coussens, L. M., Kroemer, G., & Galluzzi, L. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.06.001 · Cited by 1,837
Macrophage Polarization States in the Tumor Microenvironment
Boutilier, A. J., & Elsawa, S. F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136995 · Cited by 1,631
Cancer stem cell (CSC) resistance drivers
Najafi, M., Mortezaee, K., & Majidpoor, J. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.116781 · Cited by 466
Metabolic regulatory crosstalk between tumor microenvironment and tumor-associated macrophages
Chen, D., Zhang, X., Li, Z., & Zhu, B. (2021) · Theranostics · doi:10.7150/thno.51777 · Cited by 390
Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer
Li, C., Xu, X., Wei, S., Jiang, P., Xue, L., & Wang, J. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001341 · Cited by 360
Metadata
- Authors
- Jeong, H., Kim, S., Hong, B.-J., Lee, C.-J., Kim, Y.-E., Bok, S., Oh, J.-M., Gwak, S.-H., Yoo, M. Y., Lee, M. S., Chung, S.-J., Defrêne, J., Tessier, P., Pelletier, M., Jeon, H., Roh, T.-Y., Kim, B., Kim, K. H., Ju, J. H., Kim, S., Lee, Y.-J., Kim, D.-W., Kim, I. H., Kim, H. J., Park, J.-W., Lee, Y.-S., Lee, J. S., Cheon, G. J., Weissman, I. L., Chung, D. H., Jeon, Y. K., & Ahn, G.-O.
- Venue
- Cancer Research
- Published
- 2019-02-15
- Volume
- 79
- Issue
- 4
- Pages
- 795-806
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2908456822
- Cited by
- 268
- References
- 50
- FWCI
- 11.38
- Type
- journal article
- Language
- en
- Open access
- closed
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: Tumor-Associated Macrophages Enhance Tumor Hypoxia and Aerobic Glycolysis. https://app.cochat.ai/papers/10.1158/0008-5472.can-18-2545
- The paper
- Jeong, H., Kim, S., Hong, B.-J., Lee, C.-J., Kim, Y.-E., Bok, S., Oh, J.-M., Gwak, S.-H., Yoo, M. Y., Lee, M. S., Chung, S.-J., Defrêne, J., Tessier, P., Pelletier, M., Jeon, H., Roh, T.-Y., Kim, B., Kim, K. H., Ju, J. H., . . . Ahn, G.-O. (2019). Tumor-Associated Macrophages Enhance Tumor Hypoxia and Aerobic Glycolysis. Cancer Research. https://doi.org/10.1158/0008-5472.can-18-2545
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.
