The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1
Open accessAbstract
Macrophages (Mϕ) are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. We have recently found that tumors can alter the normal developmental process of Mϕ to trigger transient activation of monocytes in peritumoral stroma. We showed that a fraction of monocytes/Mϕ in peritumoral stroma, but not in cancer nests, expresses surface PD-L1 (also termed B7-H1) molecules in tumors from patients with hepatocellular carcinoma (HCC). Monocytes activated by tumors strongly express PD-L1 proteins with kinetics similar to their activation status, and significant correlations were found between the levels of PD-L1+ and HLA-DRhigh on tumor-infiltrating monocytes. Autocrine tumor necrosis factor α and interleukin 10 released from activated monocytes stimulated monocyte expression of PD-L1. The PD-L1+ monocytes effectively suppressed tumor-specific T cell immunity and contributed to the growth of human tumors in vivo; the effect could be reversed by blocking PD-L1 on those monocytes. Moreover, we found that PD-L1 expression on tumor-infiltrating monocytes increased with disease progression, and the intensity of the protein was associated with high mortality and reduced survival in the HCC patients. Thus, expression of PD-L1 on activated monocytes/Mϕ may represent a novel mechanism that links the proinflammatory response to immune tolerance in the tumor milieu.
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
Coussens, L. M., & Werb, Z. (2002) · Nature · doi:10.1038/nature01322 · Cited by 15,111
MANTOVANI, A., SOZZANI, S., LOCATI, M., ALLAVENA, P., & SICA, A. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02302-5 · Cited by 5,528
PD-1 and Its Ligands in Tolerance and Immunity
Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378
Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190
Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025
Ido expression by dendritic cells: tolerance and tryptophan catabolism
Mellor, A. L., & Munn, D. H. (2004) · Nature Reviews Immunology · doi:10.1038/nri1457 · Cited by 2,341
Inhibitory B7-family molecules in the tumour microenvironment
Zou, W., & Chen, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2326 · Cited by 1,608
Regulation of lung injury and repair by Toll-like receptors and hyaluronan
Jiang, D., Liang, J., Fan, J., Yu, S., Chen, S., Luo, Y., Prestwich, G. D., Mascarenhas, M. M., Garg, H. G., Quinn, D. A., et al. (2005) · Nature Medicine · doi:10.1038/nm1315 · Cited by 1,401
Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity
Curiel, T. J., Wei, S., Dong, H., Alvarez, X., Cheng, P., Mottram, P., Krzysiek, R., Knutson, K. L., Daniel, B., Zimmermann, M. C., et al. (2003) · Nature Medicine · doi:10.1038/nm863 · Cited by 1,314
Fu, J., Xu, D., Liu, Z., Shi, M., Zhao, P., Fu, B., Zhang, Z., Yang, H., Zhang, H., Zhou, C., et al. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.102 · Cited by 897
Cited by
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy
Sharma, P., Hu-Lieskovan, S., Wargo, J. A., & Ribas, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.017 · Cited by 5,588
Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment
Hanahan, D., & Coussens, L. M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.022 · Cited by 4,632
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
“Similarly, monocytes from patients with hepatocellular carcinoma express PD-L1 that contributes to human tumor xenograft growth in vivo, while the blocking of PD-L1 reverses this effect (Kuang et al., 2009).”
BackgroundMacrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840
Coordinated regulation of myeloid cells by tumours
Gabrilovich, D. I., Ostrand-Rosenberg, S., & Bronte, V. (2012) · Nature Reviews Immunology · doi:10.1038/nri3175 · Cited by 3,544
Macrophages as tools and targets in cancer therapy
Mantovani, A., Allavena, P., Marchesi, F., & Garlanda, C. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00520-5 · Cited by 1,807
Macrophages and Therapeutic Resistance in Cancer
Ruffell, B., & Coussens, L. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.02.015 · Cited by 1,474
Liver Macrophages in Tissue Homeostasis and Disease
Krenkel, O., & Tacke, F. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.11 · Cited by 1,424
Advances in immunotherapy for hepatocellular carcinoma
Sangro, B., Sarobe, P., Hervás-Stubbs, S., & Melero, I. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00438-0 · Cited by 1,306
Immune cell promotion of metastasis
Kitamura, T., Qian, B.-Z., & Pollard, J. W. (2015) · Nature Reviews Immunology · doi:10.1038/nri3789 · Cited by 1,158
Tumor-associated macrophages: an accomplice in solid tumor progression
Chen, Y., Song, Y., Du, W., Gong, L., Chang, H., & Zou, Z. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-019-0568-z · Cited by 1,096
Ruffell, B., Chang-Strachan, D., Chan, V., Rosenbusch, A., Ho, C. M. T., Pryer, N., Daniel, D., Hwang, E. S., Rugo, H. S., & Coussens, L. M. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.09.006 · Cited by 1,008
Macrophages in Tumor Microenvironments and the Progression of Tumors
Hao, N.-B., Lü, M.-H., Fan, Y.-H., Cao, Y.-L., Zhang, Z.-R., & Yang, S.-M. (2012) · Clinical and Developmental Immunology · doi:10.1155/2012/948098 · Cited by 1,003
Targeting hepatic macrophages to treat liver diseases
Tacke, F. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.02.026 · Cited by 1,003
The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Kazankov, K., Jørgensen, S. M. D., Thomsen, K. L., Møller, H. J., Vilstrup, H., George, J., Schuppan, D., & Grønbæk, H. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0082-x · Cited by 941
Tumor-associated macrophages: from basic research to clinical application
Yang, L., & Zhang, Y. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0430-2 · Cited by 847
The role of myeloid cells in cancer therapies
Engblom, C., Pfirschke, C., & Pittet, M. J. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.54 · Cited by 788
The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer
Affo, S., Yu, L.-X., & Schwabe, R. F. (2017) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-052016-100322 · Cited by 757
The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation
Bardhan, K., Anagnostou, T., & Boussiotis, V. A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00550 · Cited by 606
Ju, C., & Tacke, F. (2016) · Cellular & Molecular Immunology · doi:10.1038/cmi.2015.104 · Cited by 554
Tumor-associated macrophages: Functional diversity, clinical significance, and open questions
Biswas, S. K., Allavena, P., & Mantovani, A. (2013) · Seminars in Immunopathology · doi:10.1007/s00281-013-0367-7 · Cited by 551
Patsoukis, N., Brown, J., Petkova, V., Liu, F., Li, L., & Boussiotis, V. A. (2012) · Science Signaling · doi:10.1126/scisignal.2002796 · Cited by 529
Li, H., Wu, K., Tao, K., Chen, L., Zheng, Q., Lu, X., Liu, J., Shi, L., Liu, C., Wang, G., et al. (2012) · Hepatology · doi:10.1002/hep.25777 · Cited by 496
Liu, J., Fan, L., Yu, H., Zhang, J., He, Y., Feng, D., Wang, F., Li, X., Liu, Q., Li, Y., et al. (2019) · Hepatology · doi:10.1002/hep.30607 · Cited by 449
Self-citationThe emerging role of epigenetic therapeutics in immuno-oncology
Topper, M. J., Vaz, M., Marrone, K. A., Brahmer, J. R., & Baylin, S. B. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0266-5 · Cited by 433
Dual roles and therapeutic targeting of tumor-associated macrophages in tumor microenvironments
Xu, J., Ding, L., Mei, J., Hu, Y., Kong, X., Dai, S., Bu, T., Xiao, Q., & Ding, K. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02325-5 · Cited by 389
Self-citationXiao, X., Lao, X.-M., Chen, M.-M., Liu, R.-X., Wei, Y., Ouyang, F.-Z., Chen, D.-P., Zhao, X.-Y., Zhao, Q., Li, X.-F., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1408 · Cited by 352
Self-citationImmunity, Hypoxia, and Metabolism–the Ménage à Trois of Cancer: Implications for Immunotherapy
Riera-Domingo, C., Audigé, A., Granja, S., Cheng, W.-C., Ho, P.-C., Baltazar, F., Stockmann, C., & Mazzone, M. (2020) · Physiological Reviews · doi:10.1152/physrev.00018.2019 · Cited by 310
Li, J., Wang, L., Chen, X., Li, L., Li, Y., Ping, Y., Huang, L., Yue, D., Zhang, Z., Wang, F., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1320011 · Cited by 299
Tariq, M., Zhang, J., Liang, G., Ding, L., He, Q., & Yang, B. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25895 · Cited by 178
Self-citationAngiopoietin-2 as a Biomarker and Target for Immune Checkpoint Therapy
Wu, X., Giobbie-Hurder, A., Liao, X., Connelly, C., Connolly, E. M., Li, J., Manos, M. P., Lawrence, D., McDermott, D., Severgnini, M., et al. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0206 · Cited by 164
CD8+ T cell exhaustion and cancer immunotherapy
Wang, Q., Qin, Y., & Li, B. (2023) · Cancer Letters · doi:10.1016/j.canlet.2022.216043 · Cited by 155
Lv, Y., Zhao, Y., Wang, X., Chen, N., Mao, F., Teng, Y., Wang, T., Peng, L., Zhang, J., Cheng, P., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0530-3 · Cited by 154
Self-citationCharacterizing the role of monocytes in T cell cancer immunotherapy using a 3d microfluidic model
Lee, S. W. L., Adriani, G., Ceccarello, E., Pavesi, A., Tan, A. T., Bertoletti, A., Kamm, R. D., & Wong, S. C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00416 · Cited by 109
Poh, A. R., & Ernst, M. (2021) · Cancers · doi:10.3390/cancers13122860 · Cited by 106
The Multifaceted Roles of Macrophages in NAFLD Pathogenesis
Vonderlin, J., Chavakis, T., Sieweke, M., & Tacke, F. (2023) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2023.03.002 · Cited by 96
Increased PD-1 expression on CD4+ and CD8+ T cells is involved in immune evasion in gastric cancer
Saito, H., Kuroda, H., Matsunaga, T., Osaki, T., & Ikeguchi, M. (2013) · Journal of Surgical Oncology · doi:10.1002/jso.23281 · Cited by 94
Honda, Y., Otsuka, A., Ono, S., Yamamoto, Y., Seidel, J. A., Morita, S., Hirata, M., Kataoka, T. R., Takenouchi, T., Fujii, K., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2016.1253657 · Cited by 72
Wang, Y., Ma, R., Liu, F., Lee, S. A., & Zhang, L. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00374 · Cited by 71
NAFLD and HBV interplay - related mechanisms underlying liver disease progression
Tourkochristou, E., Assimakopoulos, S. F., Thomopoulos, K., Marangos, M., & Triantos, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.965548 · Cited by 70
Sampedro-Núñez, M., Serrano-Somavilla, A., Adrados, M., Cameselle-Teijeiro, J. M., Blanco-Carrera, C., Cabezas-Agricola, J. M., Martínez-Hernández, R., Martín-Pérez, E., Muñoz de Nova, J. L., Díaz, J. Á., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-36129-1 · Cited by 49
Immunological distinctions between nonalcoholic steatohepatitis and hepatocellular carcinoma
Koo, S.-Y., Park, E.-J., & Lee, C.-W. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0480-3 · Cited by 47
Chivu-Economescu, M., Necula, L. G., Matei, L., Dragu, D., Bleotu, C., Sorop, A., Herlea, V., Dima, S., Popescu, I., & Diaconu, C. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063214 · Cited by 42
Kohlhepp, M. S., Liu, H., Tacke, F., & Guillot, A. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1129831 · Cited by 27
Hughes, E., Lauder, S. N., Smart, K., Bloom, A., Scott, J., Jones, E., Somerville, M., Browne, M., Blainey, A., Godkin, A., et al. (2020) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-020-02603-x · Cited by 15
Metadata
- Authors
- Kuang, D.-M., Zhao, Q., Peng, C., Xu, J., Zhang, J.-P., Wu, C., & Zheng, L.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2009-05-18
- Volume
- 206
- Issue
- 6
- Pages
- 1327-1337
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2111161262
- Cited by
- 903
- References
- 12
- FWCI
- 9.42
- 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
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.
