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Biology (Basel). 2021 May 11;10(5). doi: 10.3390/biology10050425.

Characterization of Immune Cell Subsets of Tumor Infiltrating Lymphocytes in Brain Metastases.

Biology

Priyakshi Kalita-de Croft, Haarika Chittoory, Tam H Nguyen, Jodi M Saunus, Woo Gyeong Kim, Amy E McCart Reed, Malcolm Lim, Xavier M De Luca, Kaltin Ferguson, Colleen Niland, Roberta Mazzieri, Riccardo Dolcetti, Peter T Simpson, Sunil R Lakhani

Affiliations

  1. UQ Centre for Clinical Research, Faculty of Medicine, University of Queensland, Herston, QLD 4029, Australia.
  2. QIMR Berghofer Medical Research Institute, Herston, QLD 4029, Australia.
  3. Diamantina Institute, Translational, Research Institute, The University of Queensland Diamantina Institute, Brisbane, QLD 4102, Australia.
  4. Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
  5. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia.
  6. Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC 3010, Australia.
  7. Pathology Queensland, The Royal Brisbane and Women's Hospital Herston, Herston, QLD 4029, Australia.

PMID: 34064871 PMCID: PMC8150725 DOI: 10.3390/biology10050425

Abstract

The heterogeneity of tumor infiltrating lymphocytes (TILs) is not well characterized in brain metastasis. To address this, we performed a targeted analysis of immune-cell subsets in brain metastasis tissues to test immunosuppressive routes involved in brain metastasis. We performed multiplex immunofluorescence (mIF), using commercially available validated antibodies on formalin-fixed paraffin embedded whole sections. We quantitated the subsets of immune-cells utilizing a targeted panel of proteins including PanCK, CD8, CD4, VISTA and IBA-1, and analyzed an average of 15,000 cells per sample. Classifying tumors as either high (>30%) or low (<30%) TILs, we found that increased TILs density correlated with survival. Phenotyping these TILs we found tumors with low TILs had significantly higher expression of the immune-checkpoint molecule VISTA in tumor cells (

Keywords: T-cells; TILs; brain metastasis; immune checkpoint; tumor microenvironment

References

  1. Neuro Oncol. 2017 Oct 19;19(11):1511-1521 - PubMed
  2. Neuro Oncol. 2014 Apr;16(4):540-51 - PubMed
  3. Mol Med. 2012 May 09;18:519-27 - PubMed
  4. J Exp Med. 2011 Mar 14;208(3):577-92 - PubMed
  5. J Clin Pathol. 2020 Apr;73(4):197-203 - PubMed
  6. Oncoimmunology. 2015 Jun 9;5(1):e1057388 - PubMed
  7. Expert Rev Mol Diagn. 2021 Mar;21(3):323-332 - PubMed
  8. Oncol Lett. 2018 Sep;16(3):3465-3472 - PubMed
  9. Cell Rep. 2020 Jan 14;30(2):510-524.e6 - PubMed
  10. Cell. 2020 Nov 25;183(5):1234-1248.e25 - PubMed
  11. Nat Cell Biol. 2014 Sep;16(9):876-88 - PubMed
  12. Am J Pathol. 2010 Jun;176(6):2958-71 - PubMed
  13. J Neurooncol. 2016 Oct;130(1):19-29 - PubMed
  14. Nat Neurosci. 2007 Nov;10(11):1387-94 - PubMed
  15. Nature. 2015 Nov 5;527(7576):100-104 - PubMed
  16. PLoS One. 2018 Jan 17;13(1):e0186937 - PubMed
  17. Clin Cancer Res. 2018 Apr 1;24(7):1562-1573 - PubMed
  18. Adv Anat Pathol. 2017 Sep;24(5):235-251 - PubMed
  19. Cancer Immunol Immunother. 2020 Aug;69(8):1447 - PubMed
  20. Glia. 2010 Sep;58(12):1477-89 - PubMed
  21. Br J Cancer. 2019 Jan;120(1):115-127 - PubMed
  22. Cell. 2020 Jun 25;181(7):1643-1660.e17 - PubMed
  23. Oncotarget. 2017 Oct 27;8(61):103671-103681 - PubMed
  24. Glia. 2018 Dec;66(12):2645-2658 - PubMed
  25. Clin Exp Metastasis. 2013 Aug;30(6):753-68 - PubMed
  26. Cancer Immunol Immunother. 2020 Aug;69(8):1437-1446 - PubMed
  27. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Jun;28(3):748-752 - PubMed
  28. Int J Mol Sci. 2019 May 22;20(10): - PubMed
  29. J Thorac Oncol. 2019 Jul;14(7):1244-1254 - PubMed
  30. Lancet Oncol. 2018 May;19(5):672-681 - PubMed
  31. Front Oncol. 2017 Oct 30;7:251 - PubMed
  32. Oncoimmunology. 2020 Feb 17;9(1):1708065 - PubMed
  33. Cell. 2020 Jun 25;181(7):1626-1642.e20 - PubMed
  34. Cancer Immunol Immunother. 2020 Jan;69(1):33-42 - PubMed
  35. Oncogene. 2016 Jun 2;35(22):2881-92 - PubMed
  36. N Engl J Med. 2018 Aug 23;379(8):722-730 - PubMed

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