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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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Background
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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