Unraveling the peripheral and local role of inflammatory cytokines in glioblastoma survival

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art_CAVALHEIRO_Unraveling_the_peripheral_and_local_role_of_inflammatory_2023.PDF (18.24 MB)
Citações na Scopus
2
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Autores
CAMPOS, Ana Carolina P.
ROEA, Cairo Thome
DOCEMA, Marcos Fernando L.
LANCELLOTTI, Carmen Lucia P.
MARTINEZ, Raquel C. R.
PAGANO, Rosana L.
Citação
CYTOKINE, v.161, article ID 156059, 11p, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Glioblastoma (GBM) is a life-threatening disease that presents high morbidity and mortality. The standardized treatment protocol results in a global survival of less than three years in the majority of cases. Immunotherapies have gained wide recognition in cancer treatment; however, GBM has an immunosuppressive microenvironment diminishing the possible effectiveness of this therapy. In this sense, investigating the inflammatory settings and the tumoral nature of GBM patients are an important goal to create an individual plan of treatment to improve overall survival rate and quality of life of these patients. Thirty-two patients who underwent surgical resection of GBM were included in this study. Tumor samples and 10 mL of peripheral blood were collected and immediately frozen. TNF-a, IL-1a and IL-4 were evaluated in the tumor and TNF-a, IL-1a and TGF-b in the plasma by Luminex assay. Immunohistochemistry analysis to determine immune celular profile was done, including immunohisto-chemistry for CD20, CD68 and CD3. Three cases were excluded. Tumor topography, tumor nature, and tumor volume reconstructions were accurately analyzed by T1-weighted, T2-weighted, and FLAIR magnetic resonance imaging. We found that GBM patients with below median peripheral levels of TNF-a and IL-1a had a decreased survival rate when compared to above median patients. On the other hand, patients with below median pe-ripheral levels of TGF-b increased overall survival rate. Intratumoral IL-1a above median was associated with higher number of macrophages and fewer with B cells. Furthermore, plasmatic TNF-a levels were correlated with intratumoral TNF-a levels, suggesting that peripheral cytokines are related to the tumoral microenvironment. Even though tumor size has no difference regarding survival rate, we found a negative correlation between intratumoral IL-4 and tumor size, where larger tumors have less IL-4 expression. Nevertheless, the tumoral nature had a significant effect in overall survival rate, considering that infiltrative tumors showed decreased survival rate and intratumoral TNF-a. Moreover, expansive tumors revealed fewer macrophages and higher T cells. In multiple variation analyzes, we demonstrated that infiltrative tumors and below median peripheral IL-1a expression represent 3 times and 5 times hazard ratio, respectively, demonstrating a poor prognosis. Here we found that peripheral cytokines had a critical role as prognostic tools in a small cohort of GBM patients.
Palavras-chave
Glioblastoma, Magnetic resonance imaging, Cytokines, Global survival rate
URI
https://observatorio.fm.usp.br/handle/OPI/50488
Referências
  1. Bogdahn U, 2011, NEURO-ONCOLOGY, V13, P132, DOI 10.1093/neuonc/noq142
  2. Brahmer JR, 2012, NEW ENGL J MED, V366, P2455, DOI 10.1056/NEJMoa1200694
  3. da Fonseca ACC, 2013, CLIN DEV IMMUNOL, DOI 10.1155/2013/264124
  4. Chen ZH, 2018, FRONT IMMUNOL, V9, DOI 10.3389/fimmu.2018.01004
  5. Cherry JD, 2014, J NEUROINFLAMM, V11, DOI 10.1186/1742-2094-11-98
  6. Darvin P, 2018, EXP MOL MED, V50, DOI 10.1038/s12276-018-0191-1
  7. Dello Russo C, 2017, CURR CANCER DRUG TAR, V17, P267, DOI 10.2174/1568009616666160813191240
  8. Drean A, 2016, EXPERT REV NEUROTHER, V16, P1285, DOI 10.1080/14737175.2016.1202761
  9. Fu RY, 2014, MOL NEUROBIOL, V49, P1422, DOI 10.1007/s12035-013-8620-6
  10. Gabrusiewicz K, 2016, JCI INSIGHT, V1, DOI 10.1172/jci.insight.85841
  11. Goerdt S, 1999, PATHOBIOLOGY, V67, P222, DOI 10.1159/000028096
  12. Gridley DS, 1998, CANCER DETECT PREV, V22, P20, DOI 10.1046/j.1525-1500.1998.00010.x
  13. Hambardzumyan D, 2016, NAT NEUROSCI, V19, P20, DOI 10.1038/nn.4185
  14. Jha MK, 2015, NEUROSCI BIOBEHAV R, V49, P135, DOI 10.1016/j.neubiorev.2014.12.006
  15. KIRKWOOD JM, 1985, ANN INTERN MED, V103, P32, DOI 10.7326/0003-4819-103-1-32
  16. Kwon HJ, 2004, MOL CELL BIOL, V24, P9317, DOI 10.1128/MCB.24.21.9317-9326.2004
  17. Lee YJ, 1997, J IMMUNOL, V158, P2065
  18. Lee-Chang C, 2019, CANCER IMMUNOL RES, V7, P1928, DOI 10.1158/2326-6066.CIR-19-0240
  19. Lumniczky K, 2017, FRONT IMMUNOL, V8, DOI 10.3389/fimmu.2017.00517
  20. Majc B, 2021, CELLS-BASEL, V10, DOI 10.3390/cells10020265
  21. Mantovani A, 2004, TRENDS IMMUNOL, V25, P677, DOI 10.1016/j.it.2004.09.015
  22. Meini A, 2008, BRIT J PHARMACOL, V153, P1706, DOI 10.1038/bjp.2008.40
  23. OLD LJ, 1985, SCIENCE, V230, P630, DOI 10.1126/science.2413547
  24. Oshiro S, 2006, ANTICANCER RES, V26, P4027
  25. Platten M, 2001, INT J CANCER, V93, P53, DOI 10.1002/ijc.1289
  26. Press OW, 2003, BLOOD, V102, P1606, DOI 10.1182/blood-2003-01-0287
  27. Rahaman SO, 2005, CANCER RES, V65, P2956, DOI 10.1158/0008-5472.CAN-04-3592
  28. Ricklefs FL, 2018, SCI ADV, V4, DOI 10.1126/sciadv.aar2766
  29. Rutledge WC, 2013, CLIN CANCER RES, V19, P4951, DOI 10.1158/1078-0432.CCR-13-0551
  30. SATO N, 1987, J NATL CANCER I, V79, P1383
  31. Shu C, 2019, FUTURE ONCOL, V15, P1105, DOI 10.2217/fon-2018-0719
  32. Sica A, 2008, SEMIN CANCER BIOL, V18, P349, DOI 10.1016/j.semcancer.2008.03.004
  33. Silva-Filho J L, 2014, Biophys Rev, V6, P111, DOI 10.1007/s12551-013-0133-z
  34. Solinas G, 2009, J LEUKOCYTE BIOL, V86, P1065, DOI 10.1189/jlb.0609385
  35. Vig E, 1999, J BIOL CHEM, V274, P13077, DOI 10.1074/jbc.274.19.13077
  36. Warren KT, 2019, FRONT ONCOL, V9, DOI 10.3389/fonc.2019.00186
  37. Weenink B, 2020, CANCERS, V12, DOI 10.3390/cancers12030751
  38. Woroniecka K, 2018, CLIN CANCER RES, V24, P4175, DOI 10.1158/1078-0432.CCR-17-1846
  39. Xu H, 2017, FRONT AGING NEUROSCI, V9, DOI 10.3389/fnagi.2017.00352
  40. Zhou DH, 2001, INT J RADIAT BIOL, V77, P763, DOI 10.1080/09553000110050047
  41. Zhou W, 2015, J CANCER RES CLIN, V141, P575, DOI 10.1007/s00432-014-1772-6
  42. Zhu ZY, 2020, FRONT IMMUNOL, V11, DOI 10.3389/fimmu.2020.588552
  43. Zisakis A, 2007, CYTOKINE, V39, P99, DOI 10.1016/j.cyto.2007.05.012

Coleções
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - LIM/62
Artigos e Materiais de Revistas Científicas - ODS/03