Display options
Cite
Steele NG, Carpenter ES, Kemp SB, et al. Multimodal Mapping of the Tumor and Peripheral Blood Immune Landscape in Human Pancreatic Cancer. Nat Cancer. 2020;1(11):1097-1112doi: 10.1038/s43018-020-00121-4.
Steele, N. G., Carpenter, E. S., Kemp, S. B., Sirihorachai, V., The, S., Delrosario, L., Lazarus, J., Amir, E. D., Gunchick, V., Espinoza, C., Bell, S., Harris, L., Lima, F., Irizarry-Negron, V., Paglia, D., Macchia, J., Chu, A. K. Y., Schofield, H., Wamsteker, E. J., Kwon, R., Schulman, A., Prabhu, A., Law, R., Sondhi, A., Yu, J., Patel, A., Donahue, K., Nathan, H., Cho, C., Anderson, M. A., Sahai, V., Lyssiotis, C. A., Zou, W., Allen, B. L., Rao, A., Crawford, H. C., Bednar, F., Frankel, T. L., & Pasca di Magliano, M. (2020). Multimodal Mapping of the Tumor and Peripheral Blood Immune Landscape in Human Pancreatic Cancer. Nature cancer, 1(11), 1097-1112. https://doi.org/10.1038/s43018-020-00121-4
Steele, Nina G, et al. "Multimodal Mapping of the Tumor and Peripheral Blood Immune Landscape in Human Pancreatic Cancer." Nature cancer vol. 1,11 (2020): 1097-1112. doi: https://doi.org/10.1038/s43018-020-00121-4
Steele NG, Carpenter ES, Kemp SB, Sirihorachai V, The S, Delrosario L, Lazarus J, Amir ED, Gunchick V, Espinoza C, Bell S, Harris L, Lima F, Irizarry-Negron V, Paglia D, Macchia J, Chu AKY, Schofield H, Wamsteker EJ, Kwon R, Schulman A, Prabhu A, Law R, Sondhi A, Yu J, Patel A, Donahue K, Nathan H, Cho C, Anderson MA, Sahai V, Lyssiotis CA, Zou W, Allen BL, Rao A, Crawford HC, Bednar F, Frankel TL, Pasca di Magliano M. Multimodal Mapping of the Tumor and Peripheral Blood Immune Landscape in Human Pancreatic Cancer. Nat Cancer. 2020 Nov;1(11):1097-1112. doi: 10.1038/s43018-020-00121-4. Epub 2020 Oct 26. PMID: 34296197; PMCID: PMC8294470.
Copy Download .nbib Format: NLM
Share it on

Nat Cancer. 2020 Nov;1(11):1097-1112. doi: 10.1038/s43018-020-00121-4. Epub 2020 Oct 26.

Multimodal Mapping of the Tumor and Peripheral Blood Immune Landscape in Human Pancreatic Cancer.

Nature cancer

Nina G Steele, Eileen S Carpenter, Samantha B Kemp, Veerin Sirihorachai, Stephanie The, Lawrence Delrosario, Jenny Lazarus, El-Ad David Amir, Valerie Gunchick, Carlos Espinoza, Samantha Bell, Lindsey Harris, Fatima Lima, Valerie Irizarry-Negron, Daniel Paglia, Justin Macchia, Angel Ka Yan Chu, Heather Schofield, Erik-Jan Wamsteker, Richard Kwon, Allison Schulman, Anoop Prabhu, Ryan Law, Arjun Sondhi, Jessica Yu, Arpan Patel, Katelyn Donahue, Hari Nathan, Clifford Cho, Michelle A Anderson, Vaibhav Sahai, Costas A Lyssiotis, Weiping Zou, Benjamin L Allen, Arvind Rao, Howard C Crawford, Filip Bednar, Timothy L Frankel, Marina Pasca di Magliano

Affiliations

  1. Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
  2. Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor MI 48109, USA.
  3. Molecular and Cellular Pathology Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
  4. Cancer Biology Program, University of Michigan, Ann Arbor, MI 48109, USA.
  5. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  6. Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
  7. Astrolabe Diagnostics, Inc., Fort Lee, NJ, 07024, USA.
  8. Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
  9. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
  10. Michigan Institute of Data Science (MIDAS), University of Michigan, Ann Arbor, MI 48109, USA.
  11. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.

PMID: 34296197 PMCID: PMC8294470 DOI: 10.1038/s43018-020-00121-4

Abstract

Pancreatic ductal adenocarcinoma (PDA) is characterized by an immune-suppressive tumor microenvironment that renders it largely refractory to immunotherapy. We implemented a multimodal analysis approach to elucidate the immune landscape in PDA. Using a combination of CyTOF, single-cell RNA sequencing, and multiplex immunohistochemistry on patient tumors, matched blood, and non-malignant samples, we uncovered a complex network of immune-suppressive cellular interactions. These experiments revealed heterogeneous expression of immune checkpoint receptors in individual patient's T cells and increased markers of CD8

Keywords: CD8+ T cells; Single-cell RNA sequencing; TIGIT; immune checkpoints; pancreatic cancer; tumor immunology

Conflict of interest statement

Competing interests: The authors have declared that no conflict of interest exists.

References

  1. Nat Commun. 2015 Jul 22;6:7866 - PubMed
  2. Front Immunol. 2019 Jun 11;10:1315 - PubMed
  3. Nucleic Acids Res. 2012 May;40(10):4288-97 - PubMed
  4. Clin Cancer Res. 2013 Jul 1;19(13):3404-15 - PubMed
  5. Genome Res. 2009 Sep;19(9):1639-45 - PubMed
  6. Eur J Immunol. 2004 Dec;34(12):3413-22 - PubMed
  7. Cancer Res. 2007 Oct 1;67(19):9518-27 - PubMed
  8. J Immunother Cancer. 2017 Apr 18;5:33 - PubMed
  9. Nat Rev Immunol. 2019 Jun;19(6):369-382 - PubMed
  10. Cancer Res. 2014 Sep 15;74(18):5057-69 - PubMed
  11. N Engl J Med. 2012 Jun 28;366(26):2455-65 - PubMed
  12. Front Immunol. 2018 Dec 18;9:2981 - PubMed
  13. Cancer Immunol Res. 2014 May;2(5):423-35 - PubMed
  14. Nat Commun. 2017 Apr 27;8:15095 - PubMed
  15. J Exp Med. 2017 Mar 6;214(3):579-596 - PubMed
  16. Cancer Immunol Res. 2017 Nov;5(11):978-991 - PubMed
  17. Cancer Cell. 2020 Mar 16;37(3):289-307.e9 - PubMed
  18. Cell Rep. 2017 Jul 18;20(3):558-571 - PubMed
  19. Cell. 2019 Oct 31;179(4):829-845.e20 - PubMed
  20. Nature. 2017 Nov 23;551(7681):512-516 - PubMed
  21. Cancer Discov. 2019 Aug;9(8):1102-1123 - PubMed
  22. Cell. 2018 Nov 1;175(4):1031-1044.e18 - PubMed
  23. Gut. 2017 Jan;66(1):124-136 - PubMed
  24. Cell Mol Gastroenterol Hepatol. 2019;8(4):656-658.e6 - PubMed
  25. Trends Immunol. 2017 Jan;38(1):20-28 - PubMed
  26. Gut. 2018 Jun;67(6):1112-1123 - PubMed
  27. J Immunol. 2002 Aug 1;169(3):1444-52 - PubMed
  28. Nat Immunol. 2009 Jan;10(1):48-57 - PubMed
  29. Blood Adv. 2020 Apr 14;4(7):1388-1406 - PubMed
  30. JCI Insight. 2018 Jul 26;3(14): - PubMed
  31. Nat Immunol. 2017 Dec;18(12):1332-1341 - PubMed
  32. Immunity. 2017 Aug 15;47(2):323-338.e6 - PubMed
  33. Clin Cancer Res. 2017 Jun 15;23(12):3129-3138 - PubMed
  34. F1000Res. 2017 May 26;6:748 - PubMed
  35. Nature. 2012 Nov 8;491(7423):259-63 - PubMed
  36. Cancer Immunol Immunother. 2018 Nov;67(11):1659-1667 - PubMed
  37. Front Immunol. 2019 Dec 13;10:2895 - PubMed
  38. Sci Transl Med. 2019 Jul 3;11(499): - PubMed
  39. Cancer Discov. 2020 Feb;10(2):232-253 - PubMed
  40. Immunity. 2007 Oct;27(4):670-84 - PubMed
  41. Nat Immunol. 2018 Jul;19(7):723-732 - PubMed
  42. Bioinformatics. 2010 Jan 1;26(1):139-40 - PubMed
  43. Cancer Cell. 2018 Apr 9;33(4):563-569 - PubMed
  44. Curr Opin Immunol. 2017 Apr;45:43-51 - PubMed
  45. Science. 2011 May 6;332(6030):687-96 - PubMed
  46. Nature. 2019 Dec;576(7787):465-470 - PubMed
  47. Nat Rev Genet. 2019 May;20(5):257-272 - PubMed
  48. Nature. 2006 Jul 20;442(7100):299-302 - PubMed
  49. Cancer Immunol Immunother. 2017 Dec;66(12):1609-1617 - PubMed
  50. Nat Biotechnol. 2020 Mar;38(3):333-342 - PubMed
  51. Cytometry A. 2015 Jul;87(7):636-45 - PubMed
  52. Cell. 2019 Jun 27;178(1):160-175.e27 - PubMed
  53. J Immunother. 2010 Oct;33(8):828-33 - PubMed
  54. Gastroenterology. 2020 Apr;158(5):1417-1432.e11 - PubMed
  55. Cancer Discov. 2020 Mar;10(3):422-439 - PubMed
  56. Gastroenterology. 2015 Jul;149(1):201-10 - PubMed
  57. Nat Rev Clin Oncol. 2014 Nov;11(11):630-2 - PubMed
  58. Eur J Immunol. 2007 Jan;37(1):54-65 - PubMed
  59. JCI Insight. 2018 Nov 15;3(22): - PubMed
  60. Immunology. 2018 May;154(1):3-20 - PubMed
  61. Cell Rep. 2017 Apr 4;19(1):203-217 - PubMed
  62. Gut. 2014 Nov;63(11):1769-81 - PubMed
  63. Cancer Res. 2020 Mar 1;80(5):1088-1101 - PubMed

Publication Types

Grant support