The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Lack of immunoediting in murine pancreatic cancer reversed with neoantigen
Open accessAbstract
In carcinogen-driven cancers, a high mutational burden results in neoepitopes that can be recognized immunologically. Such carcinogen-induced tumors may evade this immune response through "immunoediting," whereby tumors adapt to immune pressure and escape T cell-mediated killing. Many tumors lack a high neoepitope burden, and it remains unclear whether immunoediting occurs in such cases. Here, we evaluated T cell immunity in an autochthonous mouse model of pancreatic cancer and found a low mutational burden, absence of predicted neoepitopes derived from tumor mutations, and resistance to checkpoint immunotherapy. Spontaneous tumor progression was identical in the presence or absence of T cells. Moreover, tumors arising in T cell-depleted mice grew unchecked in immune-competent hosts. However, introduction of the neoantigen ovalbumin (OVA) led to tumor rejection and T cell memory, but this did not occur in OVA immune-tolerant mice. Thus, immunoediting does not occur in this mouse model - a likely consequence, not a cause, of absent neoepitopes. Because many human tumors also have a low missense mutational load and minimal neoepitope burden, our findings have clinical implications for the design of immunotherapy for patients with such tumors.
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Citations
Cites
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Genomic analyses identify molecular subtypes of pancreatic cancer
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., et al. (2016) · Nature · doi:10.1038/nature16965 · Cited by 3,621 · cited 1×
“In KPC mice, antitumor T cell immunity is barely measurable (17) and effector T cell infiltration into tumors is minimal at even the earliest stage of neoplasia (12, 13, 18) — similar to the dearth of T cells observed histologically in other oncogene-driven cancer GEMMs (19, 20) and in the majority of human PDA (21).”
BackgroundMelanoma-intrinsic β-catenin signalling prevents anti-tumour immunity
Spranger, S., Bao, R., & Gajewski, T. F. (2015) · Nature · doi:10.1038/nature14404 · Cited by 2,830
Whole genomes redefine the mutational landscape of pancreatic cancer
Initiative, A. P. C. G., Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., et al. (2015) · Nature · doi:10.1038/nature14169 · Cited by 2,642
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Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens
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“To assess whether the negative immune checkpoint molecules PD-1 and CTLA-4 were influencing tumor rejection, as observed in the MCA model (24), we also repeated these experiments in the presence of mAb blocking”
BackgroundDynamics of the immune reaction to pancreatic cancer from inception to invasion
Clark, C. E., Hingorani, S. R., Mick, R., Combs, C., Tuveson, D. A., & Vonderheide, R. H. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0175 · Cited by 990
Self-citationBayne, L. J., Beatty, G. L., Jhala, N., Clark, C. E., Rhim, A. D., Stanger, B. Z., & Vonderheide, R. H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.025 · Cited by 947 · cited 1×
“Whole pancreata of KPC mice or subcutaneous tumors were dissected and processed as previously described (39).”
MethodSelf-citationSkoulidis, F., Byers, L. A., Diao, L., Papadimitrakopoulou, V. A., Tong, P., Izzo, J., Behrens, C., Kadara, H., Parra, E. R., Canales, J. R., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1236 · Cited by 936
Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia
Pylayeva-Gupta, Y., Lee, K. E., Hajdu, C. H., Miller, G., & Bar-Sagi, D. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.024 · Cited by 721
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
Self-citationMartinez, M., & Moon, E. K. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00128 · Cited by 851
Challenges and Opportunities for Pancreatic Cancer Immunotherapy
Bear, A. S., Vonderheide, R. H., & O'Hara, M. H. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.08.004 · Cited by 674
Self-citationBroadening the Impact of Immunotherapy to Pancreatic Cancer: Challenges and Opportunities
Balachandran, V. P., Beatty, G. L., & Dougan, S. K. (2019) · Gastroenterology · doi:10.1053/j.gastro.2018.12.038 · Cited by 444
Zhang, Y., Lazarus, J., Steele, N. G., Yan, W., Lee, H.-J., Nwosu, Z. C., Halbrook, C. J., Menjivar, R. E., Kemp, S. B., Sirihorachai, V. R., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0958 · Cited by 385
Metadata
- Authors
- Evans, R. A., Diamond, M. S., Rech, A. J., Chao, T., Richardson, M. W., Lin, J. H., Bajor, D. L., Byrne, K. T., Stanger, B. Z., Riley, J. L., Markosyan, N., Winograd, R., & Vonderheide, R. H.
- Venue
- JCI Insight
- Published
- 2016-09-08
- Volume
- 1
- Issue
- 14
- ISSN
- 2379-3708 (ISSN-L)
- OpenAlex
- W2510426677
- Cited by
- 180
- References
- 13
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- gold
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- Evans, R. A., Diamond, M. S., Rech, A. J., Chao, T., Richardson, M. W., Lin, J. H., Bajor, D. L., Byrne, K. T., Stanger, B. Z., Riley, J. L., Markosyan, N., Winograd, R., & Vonderheide, R. H. (2016). Lack of immunoediting in murine pancreatic cancer reversed with neoantigen. JCI Insight. https://doi.org/10.1172/jci.insight.88328
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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