Lack of immunoediting in murine pancreatic cancer reversed with neoantigen

JCI Insight

Volumn 1, Issue 14, 2016, Pages

  Evans, Rebecca A ^a   Diamond, Mark S ^a   Rech, Andrew J ^a   Chao, Timothy ^a   Richardson, Max W ^a   Lin, Jeffrey H ^a   Bajor, David L ^a   Byrne, Katelyn T ^a   Stanger, Ben Z ^a   Riley, James L ^a   Markosyan, Nune ^a   Winograd, Rafael ^a   Vonderheide, Robert H ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85055601829     PISSN: None     EISSN: 23793708     Source Type: Journal    
DOI: 10.1172/jci.insight.88328     Document Type: Article

References (46)

1. Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348(6230):56–61.
2. Shankaran V, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001;410(6832):1107–1111.
3. Matsushita H, et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature. 2012;482(7385):400–404.
4. Zhang B, et al. Immune surveillance and therapy of lymphomas driven by Epstein-Barr virus protein LMP1 in a mouse model. Cell. 2012;148(4):739–751.
5. Willimsky G, Blankenstein T. Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature. 2005;437(7055):141–146.
6. Casanovas O, Hicklin DJ, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell. 2005;8(4):299–309.
7. DeNardo DG, et al. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16(2):91–102.
8. Ciampricotti M, et al. Development of metastatic HER2(+) breast cancer is independent of the adaptive immune system. J Pathol. 2011;224(1):56–66.
9. Ciampricotti M, Hau CS, Doornebal CW, Jonkers J, de Visser KE. Chemotherapy response of spontaneous mammary tumors is independent of the adaptive immune system. Nat Med. 2012;18(3):344–6; author reply 346.
10. Vonderheide RH, Bayne LJ. Inflammatory networks and immune surveillance of pancreatic carcinoma. Curr Opin Immunol. 2013;25(2):200–205.
11. Joyce JA, Fearon DT. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015;348(6230):74–80.
12. Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA, Vonderheide RH. Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res. 2007;67(19):9518–9527.
13. Clark CE, Beatty GL, Vonderheide RH. Immunosurveillance of pancreatic adenocarcinoma: insights from genetically engineered mouse models of cancer. Cancer Lett. 2009;279(1):1–7.
14. Hingorani SR, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell. 2005;7(5):469–483.
15. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–2921.
16. Winograd R, et al. Induction of T-cell Immunity Overcomes Complete Resistance to PD-1 and CTLA-4 Blockade and Improves Survival in Pancreatic Carcinoma. Cancer Immunol Res. 2015;3(4):399–411.
17. Feig C, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A. 2013;110(50):20212–20217.
18. Beatty GL, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011;331(6024):1612–1616.
19. Akbay EA, et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013;3(12):1355–1363.
20. Skoulidis F, et al. Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities. Cancer Discov. 2015;5(8):860–877.
21. Bailey P, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531(7592):47–52.
22. DuPage M, Mazumdar C, Schmidt LM, Cheung AF, Jacks T. Expression of tumour-specific antigens underlies cancer immunoediting. Nature. 2012;482(7385):405–409.
23. Lo A, et al. Tumor-promoting desmoplasia is disrupted by depleting FAP-expressing stromal cells. Cancer Res. 2015;75(14):2800–2810.
24. Gubin MM, et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature. 2014;515(7528):577–581.
25. DuPage M, et al. Endogenous T cell responses to antigens expressed in lung adenocarcinomas delay malignant tumor progression. Cancer Cell. 2011;19(1):72–85.
26. Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature. 2015;523(7559):231–235.
27. Wölfel T, et al. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science. 1995;269(5228):1281–1284.
28. Robbins PF, et al. A mutated beta-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. J Exp Med. 1996;183(3):1185–1192.
29. Dubey P, et al. The immunodominant antigen of an ultraviolet-induced regressor tumor is generated by a somatic point mutation in the DEAD box helicase p68. J Exp Med. 1997;185(4):695–705.
30. Westcott PM, et al. The mutational landscapes of genetic and chemical models of Kras-driven lung cancer. Nature. 2015;517(7535):489–492.
31. Jones S, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321(5897):1801–1806.
32. Waddell N, et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature. 2015;518(7540):495–501.
33. Sausen M, et al. Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients. Nat Commun. 2015;6:7686.
34. Castle JC, et al. Exploiting the mutanome for tumor vaccination. Cancer Res. 2012;72(5):1081–1091.
35. Wang L, Pino-Lagos K, de Vries VC, Guleria I, Sayegh MH, Noelle RJ. Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3+CD4+ regulatory T cells. Proc Natl Acad Sci U S A. 2008;105(27):9331–9336.
36. Rötzschke O, et al. Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature. 1990;348(6298):252–254.
37. Ehst BD, Ingulli E, Jenkins MK. Development of a novel transgenic mouse for the study of interactions between CD4 and CD8 T cells during graft rejection. Am J Transplant. 2003;3(11):1355–1362.
38. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15(8):486–499.
39. Bayne LJ, et al. Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell. 2012;21(6):822–835.
40. Pylayeva-Gupta Y, Lee KE, Hajdu CH, Miller G, Bar-Sagi D. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell. 2012;21(6):836–847.
41. Gunderson AJ, et al. Bruton tyrosine kinase-dependent immune cell cross-talk drives pancreas cancer. Cancer Discov. 2016;6(3):270–285.
42. Ryan SO, Gantt KR, Finn OJ. Tumor antigen-based immunotherapy and immunoprevention of cancer. Int Arch Allergy Immunol. 2007;142(3):179–189.
43. Cobbold M, et al. MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia. Sci Transl Med. 2013;5(203):203ra125.
44. Foley K, et al. Current progress in immunotherapy for pancreatic cancer [published online ahead of print December 23, 2015]. Cancer Lett. doi: 10.1016/j.canlet.2015.12.020.
45. Byrne KT, Vonderheide RH. CD40 stimulation obviates innate sensors and drives T cell immunity in cancer. Cell Rep. 2016;15(12):2719–2732.
46. Cibulskis K, et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol. 2013;31(3):213–219.