Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression
IntroductionThe tumor microenvironment (TME) of glioblastoma (GB) is characterized by an increased infiltration of immunosuppressive cells that attenuate the antitumor immune response. The participation of neutrophils in tumor progression is still controversial and a dual role in the TME has been pr...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183465/full |
| _version_ | 1797821438374182912 |
|---|---|
| author | Dominique S. Rubenich Priscila O. de Souza Natalia Omizzollo Mariana R. Aubin Paulo J. Basso Luisa M. Silva Eloisa M. da Silva Fernanda C. Teixeira Gabriela F.S. Gentil Jordana L. Domagalski Maico T. Cunha Kerolainy A. Gadelha Leonardo F. Diel Nicolly E. Gelsleichter Aline S. Rubenich Gabriela S. Lenz Aline M. de Abreu Giselle M. Kroeff Ana H. Paz Fernanda Visioli Marcelo L. Lamers Marcia R. Wink Paulo V. Worm Anelise B. Araújo Jean Sévigny Jean Sévigny Niels O. S. Câmara Nils Ludwig Elizandra Braganhol |
| author_facet | Dominique S. Rubenich Priscila O. de Souza Natalia Omizzollo Mariana R. Aubin Paulo J. Basso Luisa M. Silva Eloisa M. da Silva Fernanda C. Teixeira Gabriela F.S. Gentil Jordana L. Domagalski Maico T. Cunha Kerolainy A. Gadelha Leonardo F. Diel Nicolly E. Gelsleichter Aline S. Rubenich Gabriela S. Lenz Aline M. de Abreu Giselle M. Kroeff Ana H. Paz Fernanda Visioli Marcelo L. Lamers Marcia R. Wink Paulo V. Worm Anelise B. Araújo Jean Sévigny Jean Sévigny Niels O. S. Câmara Nils Ludwig Elizandra Braganhol |
| author_sort | Dominique S. Rubenich |
| collection | DOAJ |
| description | IntroductionThe tumor microenvironment (TME) of glioblastoma (GB) is characterized by an increased infiltration of immunosuppressive cells that attenuate the antitumor immune response. The participation of neutrophils in tumor progression is still controversial and a dual role in the TME has been proposed. In this study, we show that neutrophils are reprogrammed by the tumor to ultimately promote GB progression.MethodsUsing in vitro and in vivo assays, we demonstrate the existence of bidirectional GB and neutrophil communication, directly promoting an immunosuppressive TME. Results and discussionNeutrophils have shown to play an important role in tumor malignancy especially in advanced 3D tumor model and Balb/c nude mice experiments, implying a time- and neutrophil concentration-dependent modulation. Studying the tumor energetic metabolism indicated a mitochondria mismatch shaping the TME secretome. The given data suggests a cytokine milieu in patients with GB that favors the recruitment of neutrophils, sustaining an anti-inflammatory profile which is associated with poor prognosis. Besides, glioma-neutrophil crosstalk has sustained a tumor prolonged activation via NETs formation, indicating the role of NFκB signaling in tumor progression. Moreover, clinical samples have indicated that neutrophil-lymphocyte ratio (NLR), IL-1β, and IL-10 are associated with poor outcomes in patients with GB. ConclusionThese results are relevant for understanding how tumor progression occurs and how immune cells can help in this process. |
| first_indexed | 2024-03-13T09:52:42Z |
| format | Article |
| id | doaj.art-952198285d614d539b2e02451d0e6723 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T09:52:42Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-952198285d614d539b2e02451d0e67232023-05-24T06:10:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11834651183465Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progressionDominique S. Rubenich0Priscila O. de Souza1Natalia Omizzollo2Mariana R. Aubin3Paulo J. Basso4Luisa M. Silva5Eloisa M. da Silva6Fernanda C. Teixeira7Gabriela F.S. Gentil8Jordana L. Domagalski9Maico T. Cunha10Kerolainy A. Gadelha11Leonardo F. Diel12Nicolly E. Gelsleichter13Aline S. Rubenich14Gabriela S. Lenz15Aline M. de Abreu16Giselle M. Kroeff17Ana H. Paz18Fernanda Visioli19Marcelo L. Lamers20Marcia R. Wink21Paulo V. Worm22Anelise B. Araújo23Jean Sévigny24Jean Sévigny25Niels O. S. Câmara26Nils Ludwig27Elizandra Braganhol28Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilLaboratório de Células, Tecidos e Genes, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, BrazilDepartamento de Imunologia, Universidade de São Paulo (USP), São Paulo, BrazilDepartamento de Imunologia, Universidade de São Paulo (USP), São Paulo, BrazilDepartamento de Imunologia, Universidade de São Paulo (USP), São Paulo, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilFaculdade de Odontologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilLaboratório de Células, Tecidos e Genes, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, BrazilLaboratório de Células, Tecidos e Genes, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, BrazilDepartamento de Ciências Morfológicas (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilServiço de Neurocirurgia, Hospital São José, Irmandade Santa Casa de Misericórdia de Porto Alegre (ISCMPA), Departamento de Cirurgia-Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilLaboratório de Células, Tecidos e Genes, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, BrazilCentre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec, Université Laval, Québec City, QC, CanadaDépartement de Microbiologie-Infectiologie et d’Immunologie, Faculté de Médecine, Université Laval, Québec City, QC, CanadaDepartamento de Imunologia, Universidade de São Paulo (USP), São Paulo, BrazilDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, GermanyPrograma de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, BrazilIntroductionThe tumor microenvironment (TME) of glioblastoma (GB) is characterized by an increased infiltration of immunosuppressive cells that attenuate the antitumor immune response. The participation of neutrophils in tumor progression is still controversial and a dual role in the TME has been proposed. In this study, we show that neutrophils are reprogrammed by the tumor to ultimately promote GB progression.MethodsUsing in vitro and in vivo assays, we demonstrate the existence of bidirectional GB and neutrophil communication, directly promoting an immunosuppressive TME. Results and discussionNeutrophils have shown to play an important role in tumor malignancy especially in advanced 3D tumor model and Balb/c nude mice experiments, implying a time- and neutrophil concentration-dependent modulation. Studying the tumor energetic metabolism indicated a mitochondria mismatch shaping the TME secretome. The given data suggests a cytokine milieu in patients with GB that favors the recruitment of neutrophils, sustaining an anti-inflammatory profile which is associated with poor prognosis. Besides, glioma-neutrophil crosstalk has sustained a tumor prolonged activation via NETs formation, indicating the role of NFκB signaling in tumor progression. Moreover, clinical samples have indicated that neutrophil-lymphocyte ratio (NLR), IL-1β, and IL-10 are associated with poor outcomes in patients with GB. ConclusionThese results are relevant for understanding how tumor progression occurs and how immune cells can help in this process.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183465/fulltumor associated neutrophilsglioblastomatumor microenvironmentcancerneutrophil extracellular traps |
| spellingShingle | Dominique S. Rubenich Priscila O. de Souza Natalia Omizzollo Mariana R. Aubin Paulo J. Basso Luisa M. Silva Eloisa M. da Silva Fernanda C. Teixeira Gabriela F.S. Gentil Jordana L. Domagalski Maico T. Cunha Kerolainy A. Gadelha Leonardo F. Diel Nicolly E. Gelsleichter Aline S. Rubenich Gabriela S. Lenz Aline M. de Abreu Giselle M. Kroeff Ana H. Paz Fernanda Visioli Marcelo L. Lamers Marcia R. Wink Paulo V. Worm Anelise B. Araújo Jean Sévigny Jean Sévigny Niels O. S. Câmara Nils Ludwig Elizandra Braganhol Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression Frontiers in Immunology tumor associated neutrophils glioblastoma tumor microenvironment cancer neutrophil extracellular traps |
| title | Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression |
| title_full | Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression |
| title_fullStr | Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression |
| title_full_unstemmed | Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression |
| title_short | Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression |
| title_sort | tumor neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression |
| topic | tumor associated neutrophils glioblastoma tumor microenvironment cancer neutrophil extracellular traps |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183465/full |
| work_keys_str_mv | AT dominiquesrubenich tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT priscilaodesouza tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT nataliaomizzollo tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT marianaraubin tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT paulojbasso tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT luisamsilva tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT eloisamdasilva tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT fernandacteixeira tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT gabrielafsgentil tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT jordanaldomagalski tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT maicotcunha tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT kerolainyagadelha tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT leonardofdiel tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT nicollyegelsleichter tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT alinesrubenich tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT gabrielaslenz tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT alinemdeabreu tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT gisellemkroeff tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT anahpaz tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT fernandavisioli tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT marcelollamers tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT marciarwink tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT paulovworm tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT anelisebaraujo tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT jeansevigny tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT jeansevigny tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT nielsoscamara tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT nilsludwig tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression AT elizandrabraganhol tumorneutrophilcrosstalkpromotesinvitroandinvivoglioblastomaprogression |