In Situ Overexpression of Matricellular Mechanical Proteins Demands Functional Immune Signature and Mitigates Non-Small Cell Lung Cancer Progression

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art_YAEGASHI_In_Situ_Overexpression_of_Matricellular_Mechanical_Proteins_Demands_2021.PDF (18.74 MB)
Citações na Scopus
3
Tipo de produção
article
Data de publicação
2021
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Autores
PRIETO, Tabatha Gutierrez
Citação
FRONTIERS IN IMMUNOLOGY, v.12, 2021
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Non-small cell lung carcinoma (NSCLC) is a complex cancer biome composed of malignant cells embedded in a sophisticated tumor microenvironment (TME) combined with different initiating cell types, including immune cells and cancer-associated fibroblasts (CAFs), and extracellular matrix (ECM) proteins. However, little is known about these tumors' immune-matricellular relationship as functional and mechanical barriers. This study investigated 120 patients with NSCLC to describe the immune-matricellular phenotypes of their TME and their relationship with malignant cells. Immunohistochemistry (IHC) was performed to characterize immune checkpoints (PD-L1, LAG-3, CTLA-4+, VISTA 1), T cells (CD3+), cytotoxic T cells (CD8(+), Granzyme B), macrophages (CD68+), regulatory T cells (FOXP3+, CD4+), natural killer cells (CD57+), and B lymphocytes (CD20+), whereas CAFs and collagen types I, III, and V were characterized by immunofluorescence (IF). We observed two distinct functional immune-cellular barriers-the first of which showed proximity between malignant cells and cytotoxic T cells, and the second of which showed distant proximity between non-cohesive nests of malignant cells and regulatory T cells. We also identified three tumor-associated matricellular barriers: the first, with a localized increase in CAFs and a low deposition of Col V, the second with increased CAFs, Col III and Col I fibers, and the third with a high amount of Col fibers and CAFs bundled and aligned perpendicularly to the tumor border. The Cox regression analysis was designed in two steps. First, we investigated the relationship between the immune-matricellular components and tumor pathological stage (I, II, and IIIA), and better survival rates were seen in patients whose tumors expressed collagen type III > 24.89 fibers/mm(2). Then, we included patients who had progressed to pathological stage IV and found an association between poor survival and tumor VISTA 1 expression > 52.86 cells/mm(2) and CD3+ <= 278.5 cells/mm(2). We thus concluded that differential patterns in the distribution of immune-matricellular phenotypes in the TME of NSCLC patients could be used in translational studies to predict new treatment strategies and improve patient outcome. These data raise the possibility that proteins with mechanical barrier function in NSCLC may be used by cancer cells to protect them from immune cell infiltration and immune-mediated destruction, which can otherwise be targeted effectively with immunotherapy or collagen therapy.
Palavras-chave
lung cancer, immune cells, collagen, cancer-associated fibroblasts, immunofluorescence, immunohistochemistry, non-small cell lung cancer
URI
https://observatorio.fm.usp.br/handle/OPI/42384
Referências
  1. Acerbi I, 2015, INTEGR BIOL-UK, V7, P1120, DOI 10.1039/c5ib00040h
  2. Afik R, 2016, J EXP MED, V213, P2315, DOI 10.1084/jem.20151193
  3. Altorki NK, 2019, NAT REV CANCER, V19, P9, DOI 10.1038/s41568-018-0081-9
  4. Balancin ML, 2020, PATHOL RES PRACT, V216, DOI 10.1016/j.prp.2020.153277
  5. Balancin ML, 2020, CANCER MED-US, V9, P4836, DOI 10.1002/cam4.3111
  6. Batista ML, 2016, J CACHEXIA SARCOPENI, V7, P37, DOI 10.1002/jcsm.12037
  7. Bissell MJ, 2011, NAT MED, V17, P320, DOI 10.1038/nm.2328
  8. Blessin NC, 2019, DIS MARKERS, V2019, DOI 10.1155/2019/5160565
  9. Bougherara H, 2015, FRONT IMMUNOL, V6, DOI 10.3389/fimmu.2015.00500
  10. Bourgot I, 2020, FRONT ONCOL, V10, DOI 10.3389/fonc.2020.01488
  11. Brcic L, 2018, VIRCHOWS ARCH, V472, P589, DOI 10.1007/s00428-018-2326-0
  12. Brodsky AS, 2016, BMC CANCER, V16, DOI 10.1186/s12885-016-2302-5
  13. Budhu S, 2017, SCI SIGNAL, V10, DOI 10.1126/scisignal.aak9702
  14. Carstens JL, 2017, NAT COMMUN, V8, DOI 10.1038/ncomms15095
  15. Champiat S, 2014, J THORAC ONCOL, V9, P144, DOI 10.1097/JTO.0000000000000074
  16. Chen Z, 2014, NAT REV CANCER, V14, P535, DOI 10.1038/nrc3775
  17. Conklin MW, 2011, AM J PATHOL, V178, P1221, DOI 10.1016/j.ajpath.2010.11.076
  18. Coussens LM, 2011, CSH PERSPECT BIOL, V3, DOI 10.1101/cshperspect.a003285
  19. Cox TR, 2021, NAT REV CANCER, V21, P217, DOI 10.1038/s41568-020-00329-7
  20. DeLong P, 2005, CANCER BIOL THER, V4, P342, DOI 10.4161/cbt.4.3.1644
  21. Devaud C, 2014, CANCER IMMUNOL IMMUN, V63, P869, DOI 10.1007/s00262-014-1581-4
  22. Durham NM, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0109080
  23. Gieniec KA, 2019, BRIT J CANCER, V121, P293, DOI 10.1038/s41416-019-0509-3
  24. Gilkes DM, 2014, NAT REV CANCER, V14, P430, DOI 10.1038/nrc3726
  25. Goldstraw P, 2016, J THORAC ONCOL, V11, P39, DOI 10.1016/j.jtho.2015.09.009
  26. Gooden MJM, 2011, BRIT J CANCER, V105, P93, DOI 10.1038/bjc.2011.189
  27. Graydon CG, 2021, FRONT IMMUNOL, V11, DOI 10.3389/fimmu.2020.615317
  28. Guo CC, 2013, J THORAC ONCOL, V8, P301, DOI 10.1097/JTO.0b013e318282def7
  29. Hanahan D, 2012, CANCER CELL, V21, P309, DOI 10.1016/j.ccr.2012.02.022
  30. Hao Q, 2013, BIOCHEM BIOPH RES CO, V430, P436, DOI 10.1016/j.bbrc.2012.11.039
  31. Herbst RS, 2018, NATURE, V553, P446, DOI 10.1038/nature25183
  32. Herbst RS, 2014, NATURE, V515, P563, DOI 10.1038/nature14011
  33. Hiraoka K, 2006, BRIT J CANCER, V94, P275, DOI 10.1038/sj.bjc.6602934
  34. Horne ZD, 2011, J SURG RES, V171, P1, DOI 10.1016/j.jss.2011.03.068
  35. Jamal-Hanjani M, 2017, NEW ENGL J MED, V376, P2109, DOI 10.1056/NEJMoa1616288
  36. Job S, 2020, HEPATOLOGY, V72, P965, DOI 10.1002/hep.31092
  37. Kai F, 2019, DEV CELL, V49, P332, DOI 10.1016/j.devcel.2019.03.026
  38. Kataki A, 2002, J LAB CLIN MED, V140, P320, DOI 10.1067/mlc.2002.128317
  39. Kilic A, 2011, J SURG RES, V167, P207, DOI 10.1016/j.jss.2009.08.029
  40. Kuczek DE, 2019, J IMMUNOTHER CANCER, V7, DOI 10.1186/s40425-019-0556-6
  41. Lal A, 2013, BREAST CANCER RES TR, V139, P381, DOI 10.1007/s10549-013-2556-4
  42. Liu WB, 2018, GENE, V665, P57, DOI 10.1016/j.gene.2018.04.066
  43. Mahajan UM, 2018, GASTROENTEROLOGY, V155, P1625, DOI 10.1053/j.gastro.2018.08.009
  44. Mariathasan S, 2018, NATURE, V554, P544, DOI 10.1038/nature25501
  45. Nicolas-Boluda A, 2021, ELIFE, V10, DOI 10.7554/eLife.58688
  46. Oudin MJ, 2016, COLD SH Q B, V81, P189, DOI 10.1101/sqb.2016.81.030817
  47. Pankova D, 2016, MOL CANCER RES, V14, P287, DOI 10.1158/1541-7786.MCR-15-0307
  48. Pietras K, 2010, EXP CELL RES, V316, P1324, DOI 10.1016/j.yexcr.2010.02.045
  49. Quail DF, 2013, NAT MED, V19, P1423, DOI 10.1038/nm.3394
  50. Ray A, 2017, BIOPHYS J, V112, P1023, DOI 10.1016/j.bpj.2017.01.007
  51. Ruffini E, 2009, ANN THORAC SURG, V87, P365, DOI 10.1016/j.athoracsur.2008.10.067
  52. Sakaguchi S, 2004, ANNU REV IMMUNOL, V22, P531, DOI 10.1146/annurev.immunol.21.120601.141122
  53. Salmon H, 2012, J CLIN INVEST, V122, P899, DOI 10.1172/JCI45817
  54. Sharma P, 2017, MOL BIOL CELL, V28, P2579, DOI 10.1091/mbc.E17-05-0305
  55. Shechter R, 2013, NAT REV IMMUNOL, V13, P206, DOI 10.1038/nri3391
  56. Tao H, 2012, LUNG CANCER, V75, P95, DOI 10.1016/j.lungcan.2011.06.002
  57. Tarver T, 2012, J CONS HLTH INTERNET, V16, P366, DOI 10.1080/15398285.2012.701177
  58. Tauriello DVF, 2018, NATURE, V554, P538, DOI 10.1038/nature25492
  59. Travis WD, 2015, J THORAC ONCOL, V10, P1243, DOI 10.1097/JTO.0000000000000630
  60. Turley SJ, 2015, NAT REV IMMUNOL, V15, P669, DOI 10.1038/nri3902
  61. Venning FA, 2015, FRONT ONCOL, V5, DOI 10.3389/fonc.2015.00224
  62. Wakabayashi O, 2003, CANCER SCI, V94, P1003, DOI 10.1111/j.1349-7006.2003.tb01392.x
  63. Willimsky G, 2005, NATURE, V437, P141, DOI 10.1038/nature03954
  64. Xia M, 2013, J INT MED RES, V41, P1002, DOI 10.1177/0300060513488504
  65. Yoon SM, 2017, WORLD J CLIN ONCOL, V8, P1, DOI 10.5306/wjco.v8.i1.1
  66. Yoshii M, 2012, BRIT J CANCER, V106, P1668, DOI 10.1038/bjc.2012.141
  67. Zhou J, 2021, LUNG CANCER, V153, P143, DOI 10.1016/j.lungcan.2021.01.010

Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/02
Artigos e Materiais de Revistas Científicas - LIM/03
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