BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expanded in vitro
ABSTRACTBacillus Calmette-Guérin (BCG), the nonpathogenic Mycobacterium bovis strain used as tuberculosis vaccine, has been successfully used as treatment for non-muscle invasive bladder cancer for decades, and suggested to potentiate cellular and humoral immune responses. However, the exact mechani...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2160094 |
| _version_ | 1797367154333450240 |
|---|---|
| author | Gloria Esteso María José Felgueres Álvaro F. García-Jiménez Christina Reyburn-Valés Alberto Benguría Enrique Vázquez Hugh T. Reyburn Nacho Aguiló Carlos Martín Eugenia Puentes Ingrid Murillo Esteban Rodríguez Mar Valés-Gómez |
| author_facet | Gloria Esteso María José Felgueres Álvaro F. García-Jiménez Christina Reyburn-Valés Alberto Benguría Enrique Vázquez Hugh T. Reyburn Nacho Aguiló Carlos Martín Eugenia Puentes Ingrid Murillo Esteban Rodríguez Mar Valés-Gómez |
| author_sort | Gloria Esteso |
| collection | DOAJ |
| description | ABSTRACTBacillus Calmette-Guérin (BCG), the nonpathogenic Mycobacterium bovis strain used as tuberculosis vaccine, has been successfully used as treatment for non-muscle invasive bladder cancer for decades, and suggested to potentiate cellular and humoral immune responses. However, the exact mechanism of action is not fully understood. We previously described that BCG mainly activated anti-tumor cytotoxic NK cells with upregulation of CD56 and a CD16+ phenotype. Now, we show that stimulation of human peripheral blood mononuclear cells with iBCG, a preparation based on BCG-Moreau, expands oligoclonal γδ T-cells, with a cytotoxic phenotype, together with anti-tumor CD56high CD16+ NK cells. We have used scRNA-seq, flow cytometry, and functional assays to characterize these BCG-activated γδ T-cells in detail. They had a high IFNγ secretion signature with expression of CD27+ and formed conjugates with bladder cancer cells. BCG-activated γδ T-cells proliferated strongly in response to minimal doses of cytokines and had anti-tumor functions, although not fully based on degranulation. BCG was sufficient to stimulate proliferation of γδ T-cells when cultured with other PBMC; however, BCG alone did not stimulate expansion of purified γδ T-cells. The characterization of these non-donor restricted lymphocyte populations, which can be expanded in vitro, could provide a new approach to prepare cell-based immunotherapy tools. |
| first_indexed | 2024-03-08T17:13:19Z |
| format | Article |
| id | doaj.art-d8013a98d0e348c39add8c2094c07125 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-03-08T17:13:19Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-d8013a98d0e348c39add8c2094c071252024-01-03T19:25:37ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2022.2160094BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expanded in vitroGloria Esteso0María José Felgueres1Álvaro F. García-Jiménez2Christina Reyburn-Valés3Alberto Benguría4Enrique Vázquez5Hugh T. Reyburn6Nacho Aguiló7Carlos Martín8Eugenia Puentes9Ingrid Murillo10Esteban Rodríguez11Mar Valés-Gómez12Department of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council, Madrid, SpainDepartment of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council, Madrid, SpainDepartment of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council, Madrid, SpainDepartment of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council, Madrid, SpainServicio de Genómica, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, SpainServicio de Genómica, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, SpainDepartment of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council, Madrid, SpainGrupo de Genética de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragon; Zaragoza, Spain and CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III; Madrid, SpainGrupo de Genética de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragon; Zaragoza, Spain and CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III; Madrid, SpainClinical Research Department y Research & Development Department, Biofabri, Grupo Zendal, O’Porriño, Pontevedra, SpainClinical Research Department y Research & Development Department, Biofabri, Grupo Zendal, O’Porriño, Pontevedra, SpainClinical Research Department y Research & Development Department, Biofabri, Grupo Zendal, O’Porriño, Pontevedra, SpainDepartment of Immunology and Oncology, National Centre for Biotechnology, Spanish National Research Council, Madrid, SpainABSTRACTBacillus Calmette-Guérin (BCG), the nonpathogenic Mycobacterium bovis strain used as tuberculosis vaccine, has been successfully used as treatment for non-muscle invasive bladder cancer for decades, and suggested to potentiate cellular and humoral immune responses. However, the exact mechanism of action is not fully understood. We previously described that BCG mainly activated anti-tumor cytotoxic NK cells with upregulation of CD56 and a CD16+ phenotype. Now, we show that stimulation of human peripheral blood mononuclear cells with iBCG, a preparation based on BCG-Moreau, expands oligoclonal γδ T-cells, with a cytotoxic phenotype, together with anti-tumor CD56high CD16+ NK cells. We have used scRNA-seq, flow cytometry, and functional assays to characterize these BCG-activated γδ T-cells in detail. They had a high IFNγ secretion signature with expression of CD27+ and formed conjugates with bladder cancer cells. BCG-activated γδ T-cells proliferated strongly in response to minimal doses of cytokines and had anti-tumor functions, although not fully based on degranulation. BCG was sufficient to stimulate proliferation of γδ T-cells when cultured with other PBMC; however, BCG alone did not stimulate expansion of purified γδ T-cells. The characterization of these non-donor restricted lymphocyte populations, which can be expanded in vitro, could provide a new approach to prepare cell-based immunotherapy tools.https://www.tandfonline.com/doi/10.1080/2162402X.2022.2160094Cancer immunologyBCGNK activationgamma delta T lymphocytesbladder cancerimmunotherapy |
| spellingShingle | Gloria Esteso María José Felgueres Álvaro F. García-Jiménez Christina Reyburn-Valés Alberto Benguría Enrique Vázquez Hugh T. Reyburn Nacho Aguiló Carlos Martín Eugenia Puentes Ingrid Murillo Esteban Rodríguez Mar Valés-Gómez BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expanded in vitro OncoImmunology Cancer immunology BCG NK activation gamma delta T lymphocytes bladder cancer immunotherapy |
| title | BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expanded in vitro |
| title_full | BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expanded in vitro |
| title_fullStr | BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expanded in vitro |
| title_full_unstemmed | BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expanded in vitro |
| title_short | BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expanded in vitro |
| title_sort | bcg activation of leukocytes is sufficient for the generation of donor independent innate anti tumor nk and γδ t cells that can be further expanded in vitro |
| topic | Cancer immunology BCG NK activation gamma delta T lymphocytes bladder cancer immunotherapy |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2160094 |
| work_keys_str_mv | AT gloriaesteso bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT mariajosefelgueres bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT alvarofgarciajimenez bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT christinareyburnvales bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT albertobenguria bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT enriquevazquez bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT hughtreyburn bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT nachoaguilo bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT carlosmartin bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT eugeniapuentes bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT ingridmurillo bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT estebanrodriguez bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro AT marvalesgomez bcgactivationofleukocytesissufficientforthegenerationofdonorindependentinnateantitumornkandgdtcellsthatcanbefurtherexpandedinvitro |