The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor Regulates Myeloid Inflammation and T Cell Immunity in Pancreatic Cancer
Open accessAbstract
Cancer-associated inflammation is thought to be a barrier to immune surveillance, particularly in pancreatic ductal adenocarcinoma (PDA). Gr-1(+) CD11b(+) cells are a key feature of cancer inflammation in PDA, but remain poorly understood. Using a genetically engineered mouse model of PDA, we show that tumor-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) is necessary and sufficient to drive the development of Gr-1(+) CD11b(+) cells that suppressed antigen-specific T cells. In vivo, abrogation of tumor-derived GM-CSF inhibited the recruitment of Gr-1(+) CD11b(+) cells to the tumor microenvironment and blocked tumor development-a finding that was dependent on CD8(+) T cells. In humans, PDA tumor cells prominently expressed GM-CSF in vivo. Thus, tumor-derived GM-CSF is an important regulator of inflammation and immune suppression within the tumor microenvironment.
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“FAK inhibition-mediated reprogramming of the stroma was shown to overcome radiation resistance and sensitize the tumors to immunotherapy175”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [175]
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Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · cited 1×
“It has become widely appreciated that tumor-associated inflammation is an enabling characteristic of cancer and contributes to tumor escape from immune destruction (Hanahan and Weinberg, 2011).”
BackgroundMyeloid-derived-suppressor cells as regulators of the immune system
Gabrilovich, D. I., & Nagaraj, S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2506 · Cited by 6,753 · cited 3×
“…system by targeting Gr-1 + CD11b + cells or the cytokines that regulate their differentiation. comprised of precursors to macrophages, dendritic cells, and granulocytes at earlier stages of differentiation (Gabrilovich and Nagaraj, 2009; Ostrand-Rosenberg and Sinha, 2009; Peranzoni et al., 2010).”
BackgroundCancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion
Schreiber, R. D., Old, L. J., & Smyth, M. J. (2011) · Science · doi:10.1126/science.1203486 · Cited by 6,474 · cited 2×
“Disruption of CD8 immunity by elements of the tumor microenvironment is thought to be a major mechanism of tumor immune escape (Schreiber et al., 2011).”
BackgroundHingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609
EMT and Dissemination Precede Pancreatic Tumor Formation
Rhim, A. D., Mirek, E. T., Aiello, N. M., Maitra, A., Bailey, J. M., McAllister, F., Reichert, M., Beatty, G. L., Rustgi, A. K., Vonderheide, R. H., et al. (2012) · Cell · doi:10.1016/j.cell.2011.11.025 · Cited by 2,136 · cited 1×
“This approach led to sensitive (>95% of all pancreatic epithelial cells) and specific labeling of pancreas epithelial-derived cells, with no stromal cells labeled (Rhim et al., 2012).”
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Ostrand‐Rosenberg, S., & Sinha, P. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0802740 · Cited by 1,777 · cited 2×
“…system by targeting Gr-1 + CD11b + cells or the cytokines that regulate their differentiation. comprised of precursors to macrophages, dendritic cells, and granulocytes at earlier stages of differentiation (Gabrilovich and Nagaraj, 2009; Ostrand-Rosenberg and Sinha, 2009; Peranzoni et al., 2010).”
Regulation of immune responses by L-arginine metabolism
Bronte, V., & Zanovello, P. (2005) · Nature Reviews Immunology · doi:10.1038/nri1668 · Cited by 1,775 · cited 2×
“…2C) and produced high levels of nitrite upon culture (Figure 2D), suggesting expression of inducible nitric oxide synthase (iNOS); both arginase and iNOS have been previously linked to immunosuppression by Gr-1 + CD11b + cells in tumor-bearing mice (Bronte and Zanovello, 2005; Ma et al., 2011).”
BackgroundCD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans
Beatty, G. L., Chiorean, E. G., Fishman, M. P., Saboury, B., Teitelbaum, U. R., Sun, W., Huhn, R. D., Song, W., Li, D., Sharp, L. L., et al. (2011) · Science · doi:10.1126/science.1198443 · Cited by 1,706 · cited 3×
“More likely in PDA, tumor-associated macrophages release IL-6 that directly affects the epithelium and promotes PanIN progression and PDA development in vivo (Beatty et al., 2011; Lesina et al., 2011).”
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“To understand if CD8 T cells from GM-CSF knockdown tumors exhibited effector functions, we evaluated tumor-infiltrating CD8 T cells for their capacity to secrete IFN-g and mobilize CD107a, the latter serving as a biomarker of lytic function (Betts et al., 2003).”
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“Other potential roles of Gr-1 + CD11b + cells in regulating tumor growth (Yang et al., 2004, 2008, 2011) appear therefore to be secondary or noncontributory to tumor growth, at least in this assay.”
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Understanding the tumor immune microenvironment (TIME) for effective therapy
Binnewies, M., Roberts, E. W., Kersten, K., Chan, V., Fearon, D. F., Merad, M., Coussens, L. M., Gabrilovich, D. I., Ostrand-Rosenberg, S., Hedrick, C. C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0014-x · Cited by 6,145
Self-citationInfluence of tumour micro-environment heterogeneity on therapeutic response
Junttila, M. R., & de Sauvage, F. J. (2013) · Nature · doi:10.1038/nature12626 · Cited by 2,694
Özdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., Zheng, X., Wu, C.-C., Simpson, T. R., Laklai, H., Sugimoto, H., Kahlert, C., Novitskiy, S. V., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.005 · Cited by 2,681
“In summary, our study, together with other ongoing efforts to elucidate pancreatic tumor immunity and immunotherapy (Bayne et al., 2012; Clark et al., 2007; Hiraoka et al., 2006; Roberts et al., 2013; Vonderheide et al., 2013), will likely offer insights into potential efficacy of combination…”
T cell exclusion, immune privilege, and the tumor microenvironment
Joyce, J. A., & Fearon, D. T. (2015) · Science · doi:10.1126/science.aaa6204 · Cited by 2,539
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer
Twyman-Saint Victor, C., Rech, A. J., Maity, A., Rengan, R., Pauken, K. E., Stelekati, E., Benci, J. L., Xu, B., Dada, H., Odorizzi, P. M., et al. (2015) · Nature · doi:10.1038/nature14292 · Cited by 2,434
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Metadata
- Authors
- Bayne, L. J., Beatty, G. L., Jhala, N., Clark, C. E., Rhim, A. D., Stanger, B. Z., & Vonderheide, R. H.
- Affiliations
- University of Pennsylvania (US)
- Abramson Cancer Center (US)
- Corresponding author
- Vonderheide, Robert H.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 21
- Issue
- 6
- Pages
- 822-835
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3575028
- OpenAlex
- W2129176863
- Cited by
- 947
- References
- 45
- Citations by year
- 2026: 49 · 2025: 44 · 2024: 47 · 2023: 72 · 2022: 83 · 2021: 82 · 2020: 91 · 2019: 63 · 2018: 59 · 2017: 65 · 2016: 78 · 2015: 60 · 2014: 68 · 2013: 77 · 2012: 9
- FWCI
- 29.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 411 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Abramson Family Cancer Research Institute
- National Institutes of Health (K08 088945, K12 CA076931)
- American Gastroenterological Association
- Cancer Research Institute
- Gabrielle’s Angel Foundation for Cancer Research
- Pennsylvania Department of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- GM-CSF, pancreatic ductal adenocarcinoma, tumor inflammation, myeloid cells, tumor microenvironment, T cell suppression, CD8+ T cells, tumor immune evasion, tumor-derived cytokines
- MeSH terms
- Adenocarcinoma, Animals, Humans, Immunohistochemistry, Inflammation, Mice, Transgenic, Pancreatic Neoplasms, T-Lymphocytes, Granulocyte-Macrophage Colony-Stimulating Factor, Mice, Knockout, CD8-Positive T-Lymphocytes, Models, Immunological, Receptors, Chemokine, Carcinoma, Pancreatic Ductal, Myeloid Cells, RNA Interference, CD11b Antigen, Cell Line, Tumor, Mice, Tumor Microenvironment
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