The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma
Open accessAbstract
CXCR2 has been suggested to have both tumor-promoting and tumor-suppressive properties. Here we show that CXCR2 signaling is upregulated in human pancreatic cancer, predominantly in neutrophil/myeloid-derived suppressor cells, but rarely in tumor cells. Genetic ablation or inhibition of CXCR2 abrogated metastasis, but only inhibition slowed tumorigenesis. Depletion of neutrophils/myeloid-derived suppressor cells also suppressed metastasis suggesting a key role for CXCR2 in establishing and maintaining the metastatic niche. Importantly, loss or inhibition of CXCR2 improved T cell entry, and combined inhibition of CXCR2 and PD1 in mice with established disease significantly extended survival. We show that CXCR2 signaling in the myeloid compartment can promote pancreatic tumorigenesis and is required for pancreatic cancer metastasis, making it an excellent therapeutic target.
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Cites
FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
Conroy, T., Desseigne, F., Ychou, M., Bouché, O., Guimbaud, R., Bécouarn, Y., Adenis, A., Raoul, J.-L., Gourgou-Bourgade, S., de la Fouchardière, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1011923 · Cited by 7,810
Genomic analyses identify molecular subtypes of pancreatic cancer
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“Indeed, when we compare our mouse tumors with human tumors, we find that Cxcr2 deletion is associated with a switch away from the poorly prognostic squamous identity (Bailey et al., 2016).”
Self-citationÖzdemir, 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
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Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network
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“For example, inflammatory signaling can promote oncogene-induced senescence (Acosta et al., 2008; Kuilman et al., 2008).”
Chemokine signaling via the CXCR2 receptor reinforces senescence
Acosta, J. C., O'Loghlen, A., Banito, A., Guijarro, M. V., Augert, A., Raguz, S., Fumagalli, M., Da Costa, M., Brown, C., Popov, N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.038 · Cited by 1,801 · cited 3×
“Of particular relevance to PDAC, are the elegant studies that show that CXCR2 reinforces RAS-mediated senescence in culture, and regulates the senescence-associated secretory phenotype (Acosta et al., 2008).”
Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer
Jacobetz, M. A., Chan, D. S., Neesse, A., Bapiro, T. E., Cook, N., Frese, K. K., Feig, C., Nakagawa, T., Caldwell, M. E., Zecchini, H. I., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-302529 · Cited by 1,120
Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis
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A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis
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Cited by
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
The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth
de Visser, K. E., & Joyce, J. A. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.016 · Cited by 4,059
Roles of the immune system in cancer: From tumor initiation to metastatic progression
Gonzalez, H., Hagerling, C., & Werb, Z. (2018) · Genes & Development · doi:10.1101/gad.314617.118 · Cited by 2,111
Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity
Veglia, F., Sanseviero, E., & Gabrilovich, D. I. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-00490-y · Cited by 1,940
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Chen, Z., Han, F., Du, Y., Shi, H., & Zhou, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01332-8 · Cited by 1,612
Metadata
- Authors
- Steele, C. W., Karim, S. A., Leach, J. D. G., Bailey, P., Upstill-Goddard, R., Rishi, L., Foth, M., Bryson, S., McDaid, K., Wilson, Z., Eberlein, C., Candido, J. B., Clarke, M., Nixon, C., Connelly, J., Jamieson, N., Carter, C. R., Balkwill, F., Chang, D. K., Evans, T. R. J., Strathdee, D., Biankin, A. V., Nibbs, R. J. B., Barry, S. T., Sansom, O. J., & Morton, J. P.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 29
- Issue
- 6
- Pages
- 832-845
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2416038770
- Cited by
- 845
- References
- 19
- FWCI
- 31.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. https://app.cochat.ai/papers/10.1016/j.ccell.2016.04.014
- The paper
- Steele, C. W., Karim, S. A., Leach, J. D. G., Bailey, P., Upstill-Goddard, R., Rishi, L., Foth, M., Bryson, S., McDaid, K., Wilson, Z., Eberlein, C., Candido, J. B., Clarke, M., Nixon, C., Connelly, J., Jamieson, N., Carter, C. R., Balkwill, F., Chang, D. K., . . . Morton, J. P. (2016). CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell. https://doi.org/10.1016/j.ccell.2016.04.014
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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.
