Receptores do Tipo Toll 2, 3 e 4 em Leucemia Linfocítica Aguda Infantil

Autores

  • Matheus Loureiro da Silva Cruz Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. https://orcid.org/0000-0002-1141-0254
  • Rafael Pereira dos Santos Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. https://orcid.org/0000-0003-0949-9648
  • Barbara Kunzler Souza Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. https://orcid.org/0000-0002-1694-1337
  • Mariane da Cunha Jaeger Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. Instituto do Câncer Infantil. Porto Alegre (RS), Brazil. https://orcid.org/0000-0002-3465-4083
  • Camila Alves da Silva Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. https://orcid.org/0000-0002-4243-7767
  • Lauro José Gregianin Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. https://orcid.org/0000-0003-0788-7858
  • Jiseh Fagundes Loss Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. https://orcid.org/0000-0002-0088-514X
  • Rebeca Ferreira Marques Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. https://orcid.org/0000-0001-6447-1029
  • Algemir Lunardi Brunetto Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. Instituto do Câncer Infantil. Porto Alegre (RS), Brazil. https://orcid.org/0000-0003-0668-6894
  • André Tesainer Brunetto Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. Instituto do Câncer Infantil. Porto Alegre (RS), Brazil. https://orcid.org/0000-0002-7958-1279
  • Rafael Roesler Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. https://orcid.org/0000-0001-6016-2261
  • Caroline Brunetto de Farias Universidade Federal do Rio Grande do Sul (UFRGS). Porto Alegre (RS), Brazil. Instituto do Câncer Infantil. Porto Alegre (RS), Brazil. https://orcid.org/0000-0002-6435-6626

DOI:

https://doi.org/10.32635/2176-9745.RBC.2023v69n3.3676

Palavras-chave:

leucemia-linfoma linfoblástico de células precursoras, receptores Toll-like

Resumo

Introdução: A leucemia linfoblástica aguda (LLA) é o tipo de câncer mais comum em crianças e representa 80% das leucemias pediátricas. Novos alvos são necessários para melhorar as taxas de sobrevivência para doença refratária e recidivante. Há evidências acumuladas de que a sinalização de receptores Toll-Like (TLR) pode estar associada a resultados em câncer, embora pouco tenha sido descrito em leucemias. Objetivo: Analisar a expressão e a contribuição dos TLR para o desenvolvimento da LLA infantil. Método: Avaliar o efeito de agonistas específicos de TLR2, TLR3 e TLR4 na viabilidade e proliferação de linhagens celulares de LLA infantil e analisar a expressão do RNAm desses tipos de TLR em células blásticas da medula óssea no diagnóstico (D0) e na indução (D35) em pacientes LLA pediátricos. Resultados: O tratamento com agonistas de TLR reduziu a viabilidade celular das linhagens celulares Jurkat e Sup-B15. A distribuição do ciclo celular em Jurkat foi alterada, reduzindo as células poliploides e aumentando a fase sub-G1. Houve aumento na expressão dos receptores entre D0 e D35 em amostras de pacientes. Conclusão: Observou-se que a viabilidade celular das linhagens celulares respondeu com diferentes sensibilidades aos agonistas. A poliploidia associada a malignidade tumoral foi reduzida, além de o aumento da fase sub-G1 indicar aumento da apoptose. Houve diferenças na expressão de TLR em D35 entre os grupos de risco da doença. Pacientes com alta expressão de TLR2 e baixa expressão de TLR4 no D35 demonstraram pior prognóstico.

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Referências

Instituto Nacional de Câncer. Estimativa 2023: incidência de câncer no Brasil. Rio de Janeiro: INCA; 2022 [acesso 2023 jul 3]. Disponível em: https://www.inca.gov.br/sites/ufu.sti.inca.local/files//media/document//estimativa-2023.pdf

National Cancer Institute (US) [Internet]. Bethesda (MD): NIH; [2023]. Childhood acute lymphoblastic leukemia treatment (PDQ®) - Health professional version; 2023 Apr 11 [cited 2022 Jun 8]. Available from: https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq

Wells G, Kennedy PT, Dahal LN. Investigating the role of indoleamine 2,3-dioxygenase in acute myeloid leukemia: a systematic review. Front Immunol. 2021;12:651687. doi: https://doi.org/10.3389/fimmu.2021.651687 DOI: https://doi.org/10.3389/fimmu.2021.651687

Rabe JL, Gardner L, Hunter R, et al. IL12 abrogates calcineurin-dependent immune evasion during leukemia progression. Cancer Res. 2019;79(14):3702-13. doi: https://doi.org/10.1158/0008-5472.CAN-18-3800 DOI: https://doi.org/10.1158/0008-5472.CAN-18-3800

Arandi N, Ramzi M, Safaei F, et al. Overexpression of indoleamine 2,3-dioxygenase correlates with regulatory T cell phenotype in acute myeloid leukemia patients with normal karyotype. Blood Res. 2018;53(4):294-8. doi: https://doi.org/10.5045/br.2018.53.4.294 DOI: https://doi.org/10.5045/br.2018.53.4.294

Favere K, Bosman M, Delputte PL, et al. A systematic literature review on the effects of exercise on human Toll-like receptor expression. Exerc Immunol Rev [Internet]. 2021 [cited 2022 Jun 10];27:84-124. Available from: https://img1.wsimg.com/blobby/go/2b32b969-f24b-4b6f-8e61-5d111c218d54/EIR%202021%20Komplett%20KO3.pdf

Sahoo BR. Structure of fish Toll-Like Receptors (TLR) and NOD-like receptors (NLR). Int J Biol Macromol. 2020;161:1602-17. doi: https://doi.org/10.1016/j.ijbiomac.2020.07.293 DOI: https://doi.org/10.1016/j.ijbiomac.2020.07.293

Ayala-Cuellar AP, Cho J, Choi KC. Toll-like receptors: a pathway alluding to cancer control. J Cell Physiol. 2019;234(12):21707-15. doi: https://doi.org/10.1002/jcp.28879 DOI: https://doi.org/10.1002/jcp.28879

Sfanos KS. Targeting Toll-like receptors in cancer prevention. Cancer Prev Res (Phila). 2018;11(5):251-4. doi: https://doi.org/10.1158/1940-6207.CAPR-18-0079 DOI: https://doi.org/10.1158/1940-6207.CAPR-18-0079

Li TT, Ogino S, Qian ZR. Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy. World J Gastroenterol. 2014;20(47):17699-708. doi: https://doi.org/10.3748/wjg.v20.i47.17699 DOI: https://doi.org/10.3748/wjg.v20.i47.17699

Iacobucci I, Papayannidis C, Lonetti A, et al. Cytogenetic and molecular predictors of outcome in acute lymphocytic leukemia: recent developments. Curr Hemat Malig Rep. 2012;7(2):133-43. doi: https://doi.org/10.1007/s11899-012-0122-5 DOI: https://doi.org/10.1007/s11899-012-0122-5

Chiron D, Bekeredjian-Ding I, Pellat-Deceunynck C, et al. Toll-like receptors: lessons to learn from normal and malignant human B cells. Blood. 2008;112(6):2205-13. doi: https://doi.org/10.1182/blood-2008-02-140673 DOI: https://doi.org/10.1182/blood-2008-02-140673

Conselho Nacional de Saúde (BR). Resolução nº 466, de 12 de dezembro de 2012. Aprova as diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. Diário Oficial da União, Brasília, DF. 2013 jun 13; Seção 1:59.

Maino E, Scattolin AM, Viero P, et al. Modern immunotherapy of adult B-lineage acute lymphoblastic leukemia with monoclonal antibodies and chimeric antigen receptor modified t cells. Mediterr J Hematol Infect Dis. 2015;7(1):e2015001. doi: https://doi.org/10.4084/MJHID.2015.001 DOI: https://doi.org/10.4084/mjhid.2015.001

Campesato LF, Silva APM, Cordeiro L, et al. High IL-1R8 expression in breast tumors promotes tumor growth and contributes to impaired antitumor immunity. Oncotarget. 2017;8(30):49470-83. doi: https://doi.org/10.18632/oncotarget.17713 DOI: https://doi.org/10.18632/oncotarget.17713

Zou W. Mechanistic insights into cancer immunity and immunotherapy. Cell Mol Immunol. 2018;15(5):419-20. doi: https://doi.org/10.1038/s41423-018-0011-5 DOI: https://doi.org/10.1038/s41423-018-0011-5

Chen Z, Wang JH. How the signaling crosstalk of B Cell Receptor (BCR) and Co-receptors regulates antibody class switch recombination: a new perspective of checkpoints of BCR signaling. Front Immunol. 2021;12:663443. doi: https://doi.org/10.3389/fimmu.2021.663443 DOI: https://doi.org/10.3389/fimmu.2021.663443

Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373-84. doi: https://doi.org/10.1038/ni.1863 DOI: https://doi.org/10.1038/ni.1863

Sivori S, Pende D, Quatrini L, et al. NK cells and ILCs in tumor immunotherapy. Mol Aspects Med. 2021;80:100870. doi: https://doi.org/10.1016/j.mam.2020.100870 DOI: https://doi.org/10.1016/j.mam.2020.100870

Collinson-Pautz MR, Chang WC, Lu A, et al. Constitutively active MyD88/CD40 costimulation enhances expansion and efficacy of chimeric antigen receptor T cells targeting hematological malignancies. Leuk. 2019;33:2195-2207. doi: https://doi.org/10.1038/s41375-019-0417-9 DOI: https://doi.org/10.1038/s41375-019-0417-9

Szymańska A, Bojarska-Junak A, Drobiecki A, et al. TLR2 expression on leukemic B cells from patients with chronic lymphocytic leukemia. Arch Immunol Ther Exp (Warsz). 2019;67(1):55-65. doi: https://doi.org/10.1007/s00005-018-0523-9 DOI: https://doi.org/10.1007/s00005-018-0523-9

Collins PE, Somma D, Kerrigan D, et al. The IκB-protein BCL-3 controls Toll-like receptor-induced MAPK activity by promoting TPL-2 degradation in the nucleus. Proc Natl Acad Sci USA. 2019;116(51):25828-38. doi: https://doi.org/10.1073/pnas.1900408116 DOI: https://doi.org/10.1073/pnas.1900408116

Spaner DE, Venema R, Huang J, et al. Association of blood IgG with tumor necrosis factor-alpha and clinical course of chronic lymphocytic leukemia. EBioMedicine. 2018;35:222-32. doi: https://doi.org/10.1016/j.ebiom.2018.08.045 DOI: https://doi.org/10.1016/j.ebiom.2018.08.045

Luo X, Zhang X, Gan L, et al. The outer membrane protein Tp92 of Treponema pallidum induces human mononuclear cell death and IL-8 secretion. J Cell Mol Med. 2018;22(12):6039-54. doi: https://doi.org/10.1111/jcmm.13879 DOI: https://doi.org/10.1111/jcmm.13879

Khajeh Alizadeh Attar M, Anwar MA, Eskian M, et al. Basic understanding and therapeutic approaches to target toll-like receptors in cancerous microenvironment and metastasis. Med Res Rev. 2018;38(5):1469-84. doi: https://doi.org/10.1002/med.21480 DOI: https://doi.org/10.1002/med.21480

Meliț LE, Mărginean CO, Mărginean CD, et al. The relationship between Toll-like receptors and Helicobacter pylori-related gastropathies: still a controversial topic. J Immunol Res. 2019;2019:8197048. doi: https://doi.org/10.1155/2019/8197048 DOI: https://doi.org/10.1155/2019/8197048

Spanou E, Kalisperati P, Pateras IS, et al. Genetic Variability as a regulator of TLR4 and NOD signaling in response to bacterial driven DNA Damage Response (DDR) and inflammation: focus on the gastrointestinal (GI) tract. Front Genet. 2017;8:65. doi: https://doi.org/10.3389/fgene.2017.00065 DOI: https://doi.org/10.3389/fgene.2017.00065

Paarnio K, Väyrynen S, Klintrup K, et al. Divergent expression of bacterial wall sensing Toll-like receptors 2 and 4 in colorectal cancer. World J Gastroenterol. 2017;23(26):4831-8. doi: https://doi.org/10.3748/wjg.v23.i26.4831 DOI: https://doi.org/10.3748/wjg.v23.i26.4831

Rybka J, Butrym A, Wróbel T, et al. The expression of Toll-like receptors in patients with B-cell chronic lymphocytic leukemia. Arch Immunol Ther Exp (Warsz). 2016;64(Suppl 1):147-50. doi: https://doi.org/10.1007/s00005-016-0433-7 DOI: https://doi.org/10.1007/s00005-016-0433-7

Rybka J, Butrym A, Wróbel T, et al. The expression of Toll-like receptors in patients with acute myeloid leukemia treated with induction chemotherapy. Leuk Res. 2015;39(3):318-22. doi: https://doi.org/10.1016/j.leukres.2015.01.002 DOI: https://doi.org/10.1016/j.leukres.2015.01.002

Sánchez-Cuaxospa M, Contreras-Ramos A, Pérez-Figueroa E, et al. Low expression of Toll-like receptors in peripheral blood mononuclear cells of pediatric patients with acute lymphoblastic leukemia. Int J Oncol. 2016;49(2):675-81. doi: https://doi.org/10.3892/ijo.2016.3569 DOI: https://doi.org/10.3892/ijo.2016.3569

Maharjan S, Park BK, Lee SI, et al. Gomisin G suppresses the growth of colon cancer cells by attenuation of AKT phosphorylation and arrest of cell cycle progression. Biomol Ther (Seoul). 2019;27(2):210-5. doi: https://doi.org/10.4062/biomolther.2018.054 DOI: https://doi.org/10.4062/biomolther.2018.054

Alonso-Lecue P, Pedro I, Coulon V, et al. Inefficient differentiation response to cell cycle stress leads to genomic instability and malignant progression of squamous carcinoma cells. Cell Death Dis. 2017;8:e2901. doi: https://doi.org/10.1038/cddis.2017.259 DOI: https://doi.org/10.1038/cddis.2017.259

Jo Y, Shin DY. Repression of the F-box protein Skp2 is essential for actin damage-induced tetraploid G1 arrest. BMB Rep. 2017;50(7):379-83. doi: https://doi.org/10.5483/bmbrep.2017.50.7.063 DOI: https://doi.org/10.5483/BMBRep.2017.50.7.063

Wang D, Xiao PL, Duan HX, et al. Peptidoglycans promotes human leukemic THP-1 cell apoptosis and differentiation. Asian Pac J Cancer Prev. 2012;13(12):6409-13. doi: https://doi.org/10.7314/apjcp.2012.13.12.6409 DOI: https://doi.org/10.7314/APJCP.2012.13.12.6409

Salaun B, Zitvogel L, Asselin-Paturel C, et al. TLR3 as a biomarker for the therapeutic efficacy of double-stranded RNA in breast cancer. Cancer Res. 2011;71(5):1607-14. doi: https://doi.org/10.1158/0008-5472.CAN-10-3490 DOI: https://doi.org/10.1158/0008-5472.CAN-10-3490

Li H, Gao C, Liu C, et al. A review of the biological activity and pharmacology of cryptotanshinone, an important active constituent in Danshen. Biomed Pharmacother. 2021;137:111332. doi: https://doi.org/10.1016/j.biopha.2021.111332 DOI: https://doi.org/10.1016/j.biopha.2021.111332

Gliozzi M, Scicchitano M, Bosco F, et al. Modulation of nitric oxide synthases by oxidized ldls: role in vascular inflammation and atherosclerosis development. Int J Mol Sci. 2019;20(13):3294. doi: https://doi.org/10.3390/ijms20133294 DOI: https://doi.org/10.3390/ijms20133294

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Publicado

2023-07-06

Como Citar

1.
Cruz ML da S, Santos RP dos, Souza BK, Jaeger M da C, Silva CA da, Gregianin LJ, Loss JF, Marques RF, Brunetto AL, Brunetto AT, Roesler R, Farias CB de. Receptores do Tipo Toll 2, 3 e 4 em Leucemia Linfocítica Aguda Infantil. Rev. Bras. Cancerol. [Internet]. 6º de julho de 2023 [citado 28º de abril de 2024];69(3):e-053676. Disponível em: https://rbc.inca.gov.br/index.php/revista/article/view/3676

Edição

v. 69 n. 3 (2023): jul./ago./set.

Seção

ARTIGO ORIGINAL

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Os direitos morais e intelectuais dos artigos pertencem aos respectivos autores, que concedem à RBC o direito de publicação.

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Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.

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