The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Bruton Tyrosine Kinase–Dependent Immune Cell Cross-talk Drives Pancreas Cancer
Open accessAbstract
Pancreas ductal adenocarcinoma (PDAC) has one of the worst 5-year survival rates of all solid tumors, and thus new treatment strategies are urgently needed. Here, we report that targeting Bruton tyrosine kinase (BTK), a key B-cell and macrophage kinase, restores T cell–dependent antitumor immune responses, thereby inhibiting PDAC growth and improving responsiveness to standard-of-care chemotherapy. We report that PDAC tumor growth depends on cross-talk between B cells and FcRγ+ tumor–associated macrophages, resulting in TH2-type macrophage programming via BTK activation in a PI3Kγ-dependent manner. Treatment of PDAC-bearing mice with the BTK inhibitor PCI32765 (ibrutinib) or by PI3Kγ inhibition reprogrammed macrophages toward a TH1 phenotype that fostered CD8+ T-cell cytotoxicity, and suppressed PDAC growth, indicating that BTK signaling mediates PDAC immunosuppression. These data indicate that pharmacologic inhibition of BTK in PDAC can reactivate adaptive immune responses, presenting a new therapeutic modality for this devastating tumor type. Significance: We report that BTK regulates B-cell and macrophage-mediated T-cell suppression in pancreas adenocarcinomas. Inhibition of BTK with the FDA-approved inhibitor ibrutinib restores T cell–dependent antitumor immune responses to inhibit PDAC growth and improves responsiveness to chemotherapy, presenting a new therapeutic modality for pancreas cancer. Cancer Discov; 6(3); 270–85. ©2015 AACR. See related commentary by Roghanian et al., p. 230. See related article by Pylayeva-Gupta et al., p. 247. See related article by Lee et al., p. 256. This article is highlighted in the In This Issue feature, p. 217
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Self-citationThe PI3K Pathway in Human Disease
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Macrophages and metabolism in the tumor microenvironment
Vitale, I., Manic, G., Coussens, L. M., Kroemer, G., & Galluzzi, L. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.06.001 · Cited by 1,837
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
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Metadata
- Authors
- Gunderson, A. J., Kaneda, M. M., Tsujikawa, T., Nguyen, A. V., Affara, N. I., Ruffell, B., Gorjestani, S., Liudahl, S. M., Truitt, M., Olson, P., Kim, G., Hanahan, D., Tempero, M. A., Sheppard, B., Irving, B., Chang, B. Y., Varner, J. A., & Coussens, L. M.
- Venue
- Cancer Discovery
- Published
- 2016-03-01
- Volume
- 6
- Issue
- 3
- Pages
- 270-285
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2293645537
- Cited by
- 486
- References
- 52
- FWCI
- 16.64
- Type
- journal article
- Language
- en
- Open access
- green
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- Gunderson, A. J., Kaneda, M. M., Tsujikawa, T., Nguyen, A. V., Affara, N. I., Ruffell, B., Gorjestani, S., Liudahl, S. M., Truitt, M., Olson, P., Kim, G., Hanahan, D., Tempero, M. A., Sheppard, B., Irving, B., Chang, B. Y., Varner, J. A., & Coussens, L. M. (2016). Bruton Tyrosine Kinase–Dependent Immune Cell Cross-talk Drives Pancreas Cancer. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-15-0827
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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.
