Antibody therapy targeting the CD47 protein is effective in a model of aggressive metastatic leiomyosarcoma
Open accessAbstract
Antibodies against CD47, which block tumor cell CD47 interactions with macrophage signal regulatory protein-α, have been shown to decrease tumor size in hematological and epithelial tumor models by interfering with the protection from phagocytosis by macrophages that intact CD47 bestows upon tumor cells. Leiomyosarcoma (LMS) is a tumor of smooth muscle that can express varying levels of colony-stimulating factor-1 (CSF1), the expression of which correlates with the numbers of tumor-associated macrophages (TAMs) that are found in these tumors. We have previously shown that the presence of TAMs in LMS is associated with poor clinical outcome and the overall effect of TAMs in LMS therefore appears to be protumorigenic. However, the use of inhibitory antibodies against CD47 offers an opportunity to turn TAMs against LMS cells by allowing the phagocytic behavior of resident macrophages to predominate. Here we show that interference with CD47 increases phagocytosis of two human LMS cell lines, LMS04 and LMS05, in vitro. In addition, treatment of mice bearing subcutaneous LMS04 and LMS05 tumors with a novel, humanized anti-CD47 antibody resulted in significant reductions in tumor size. Mice bearing LMS04 tumors develop large numbers of lymph node and lung metastases. In a unique model for neoadjuvant treatment, mice were treated with anti-CD47 antibody starting 1 wk before resection of established primary tumors and subsequently showed a striking decrease in the size and number of metastases. These data suggest that treatment with anti-CD47 antibodies not only reduces primary tumor size but can also be used to inhibit the development of, or to eliminate, metastatic disease.
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Immune cells can attenuate metastasis.
“On one hand, there is evidence that immune cells have the capability to attenuate metastasis[54–59], which provides insight into how to restore or enhance their ability to combat cancer.”
From Microfluidics: A New Tool for Modeling Cancer–Immune Interactions (2016) · cites this paper as [59]
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Cites
Macrophage Diversity Enhances Tumor Progression and Metastasis
Qian, B., & Pollard, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.03.014 · Cited by 5,208 · see citing works
Distinct role of macrophages in different tumor microenvironments
Lewis, C. E., & Pollard, J. W. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4005 · Cited by 2,225 · see citing works
Majeti, R., Chao, M. P., Alizadeh, A. A., Pang, W. W., Jaiswal, S., Gibbs, K. D., van Rooijen, N., & Weissman, I. L. (2009) · Cell · doi:10.1016/j.cell.2009.05.045 · Cited by 1,752 · see citing works
Self-citationCD47 Is Upregulated on Circulating Hematopoietic Stem Cells and Leukemia Cells to Avoid Phagocytosis
Jaiswal, S., Jamieson, C. H. M., Pang, W. W., Park, C. Y., Chao, M. P., Majeti, R., Traver, D. J., van Rooijen, N., & Weissman, I. L. (2009) · Cell · doi:10.1016/j.cell.2009.05.046 · Cited by 1,578 · see citing works
Self-citationNOD/SCID/γcnull mouse: an excellent recipient mouse model for engraftment of human cells
Ito, M., Hiramatsu, H., Kobayashi, K., Suzue, K., Kawahata, M., Hioki, K., Ueyama, Y., Koyanagi, Y., Sugamura, K., Tsuji, K., et al. (2002) · Blood · doi:10.1182/blood-2001-12-0207 · Cited by 1,483 · see citing works
Chao, M. P., Alizadeh, A. A., Tang, C. Z., Myklebust, J. H., Varghese, B., Gill, S. I., Jan, M., Cha, A. C., Chan, C. K. F., Tan, B. T., et al. (2010) · Cell · doi:10.1016/j.cell.2010.07.044 · Cited by 1,095 · see citing works
Self-citationIntegrin-associated protein (CD47) and its ligands
Brown, E. (2001) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)01906-1 · Cited by 880 · see citing works
Chao, M. P., Jaiswal, S., Weissman-Tsukamoto, R., Alizadeh, A. A., Gentles, A. J., Volkmer, J., Weiskopf, K., Willingham, S. B., Raveh, T., Park, C. Y., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001375 · Cited by 776 · see citing works
Self-citationChen, Q., Zhang, X. H.-F., & Massagué, J. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.08.025 · Cited by 619 · see citing works
The Stanford Microarray Database
Sherlock, G. J. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.152 · Cited by 534 · see citing works
The SIRP family of receptors and immune regulation
Barclay, A. N., & Brown, M. H. (2006) · Nature reviews. Immunology · doi:10.1038/nri1859 · Cited by 427 · see citing works
Cameron, M. D., Schmidt, E. E., Kerkvliet, N. I., Nadkarni, K. V., Morris, V. L., Groom, A. C., Chambers, A. F., & MacDonald, I. C. (2000) · PubMed · Cited by 400 · see citing works
M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis
Kubota, Y., Takubo, K., Shimizu, T., Ohno, H., Kishi, K., Shibuya, M., Saya, H., & Suda, T. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20081605 · Cited by 388 · see citing works
Therapeutic Antibody Targeting of CD47 Eliminates Human Acute Lymphoblastic Leukemia
Chao, M. P., Alizadeh, A. A., Tang, C. Z., Jan, M., Weissman-Tsukamoto, R., Zhao, F., Park, C. Y., Weissman, I. L., & Majeti, R. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2238 · Cited by 381 · see citing works
Self-citationClonal Analysis of Mouse Development Reveals a Polyclonal Origin for Yolk Sac Blood Islands
Ueno, H., & Weissman, I. L. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.08.001 · Cited by 245 · see citing works
Self-citationMacrophages as mediators of tumor immunosurveillance
Jaiswal, S., Chao, M. P., Majeti, R., & Weissman, I. L. (2010) · Trends in Immunology · doi:10.1016/j.it.2010.04.001 · Cited by 241 · see citing works
Self-citationBlay, J., Glabbeke, M. V., Verweij, J., et al. (2002) · European Journal of Cancer · doi:10.1016/s0959-8049(02)00480-x · Cited by 185 · see citing works
Prognostic Significance of Macrophage Infiltration in Leiomyosarcomas
Lee, C., Espinosa, Í., Vrijaldenhoven, S., Subramanian, S., Montgomery, K. D., Zhu, S., Marinelli, R. J., Peterse, J. L., Poulin, N., Nielsen, T. O., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1712 · Cited by 172 · see citing works
Self-citationDiscovery of molecular subtypes in leiomyosarcoma through integrative molecular profiling
Beck, A. H., Lee, C.-H., Witten, D., Gleason, B., Edris, B., Espinosa, Í., Zhu, S., Li, R., Montgomery, K. D., Marinelli, R. J., et al. (2009) · Oncogene · doi:10.1038/onc.2009.381 · Cited by 147 · see citing works
Self-citationEspinosa, Í., Beck, A. H., Lee, C., et al. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.081037 · Cited by 89 · see citing works
Self-citationAdell, G., Zhang, H., Evertsson, S., Sun, X., St�l, O., & Nordenskj�ld, B. (2001) · Cancer · doi:10.1002/1097-0142(20010515)91:10 · Cited by 43 · see citing works
CSF1 Expression in Nongynecological Leiomyosarcoma Is Associated with Increased Tumor Angiogenesis
Espinosa, Í., Edris, B., Lee, C., et al. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.06.021 · Cited by 38 · see citing works
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Research works printed but not linked: 1
- [1]1. Evans HL, Shipley J (2002) Pathology and Genetics of Tumours of Soft Tissue and Bone - World Health Organization Classification of Tumours, eds Fletcher CDM, Unni KK, Mertens F (IARC Press, Lyon), pp 131-134.
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Zanganeh, S., Hutter, G., Spitler, R., Lenkov, O., Mahmoudi, M., Shaw, A., Pajarinen, J. S., Nejadnik, H., Goodman, S., Moseley, M., et al. (2016) · Nature Nanotechnology · doi:10.1038/nnano.2016.168 · Cited by 1,647 · see citing works
Microfluidics: A New Tool for Modeling Cancer–Immune Interactions
Boussommier-Calleja, A., Li, R., Chen, M. B., Wong, S. C., & Kamm, R. D. (2016) · Trends in Cancer · doi:10.1016/j.trecan.2015.12.003 · Cited by 224 · see citing works
Autophagy proteins regulate cell engulfment mechanisms that participate in cancer
Kim, S. E., & Overholtzer, M. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.05.004 · Cited by 35 · see citing works
- Authors
- Edris, B., Weiskopf, K., Volkmer, A. K., Volkmer, J.-P., Willingham, S. B., Contreras-Trujillo, H., Liu, J., Majeti, R., West, R. B., Fletcher, J. A., Beck, A. H., Weissman, I. L., & van de Rijn, M.
- Affiliations
- Stanford Medicine (US)
- Department of Pathology, and
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-03-26
- Volume
- 109
- Issue
- 17
- Pages
- 6656-6661
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3340056
- OpenAlex
- W2057774884
- Cited by
- 258
- References
- 22
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 18 · 2023: 18 · 2022: 28 · 2021: 23 · 2020: 25 · 2019: 19 · 2018: 22 · 2017: 25 · 2016: 16 · 2015: 20 · 2014: 12 · 2013: 13 · 2012: 7
- FWCI
- 7.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Ludwig Institute for Cancer Research
- National Institutes of Health
- National Cancer Institute (CA 112270, R01CA112270)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Keywords
- CD47, anti-CD47 antibody, leiomyosarcoma, tumor-associated macrophages, phagocytosis, metastasis, colony-stimulating factor 1, neoadjuvant therapy, humanized monoclonal antibody, cancer immunotherapy
- MeSH terms
- Animals, Antibodies, Disease Models, Animal, Immunotherapy, Leiomyosarcoma, Neoplasm Metastasis, Phagocytosis, Cell Line, Tumor, Mice, CD47 Antigen
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