CD4+ T Cells Mediate Dendritic Cell Licensing to Promote Multi‐Antigen Anti‐Leukemic Immune Response
ABSTRACT Background Single antigen (Ag)‐targeted immunotherapies for acute lymphoblastic leukemia (ALL) are highly effective; however, up to 50% of patients relapse after these treatments. Most of these relapses lack target Ag expression, suggesting targeting multiple Ags would be advantageous. Mate...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70508 |
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| author | Luis Gil‐de‐Gómez Joseph J. Mattei Jessica H. Lee Stephan A. Grupp Gregor S. D. Reid Alix E. Seif |
| author_facet | Luis Gil‐de‐Gómez Joseph J. Mattei Jessica H. Lee Stephan A. Grupp Gregor S. D. Reid Alix E. Seif |
| author_sort | Luis Gil‐de‐Gómez |
| collection | DOAJ |
| description | ABSTRACT Background Single antigen (Ag)‐targeted immunotherapies for acute lymphoblastic leukemia (ALL) are highly effective; however, up to 50% of patients relapse after these treatments. Most of these relapses lack target Ag expression, suggesting targeting multiple Ags would be advantageous. Materials & Methods The multi‐Ag immune responses to ALL induced by transducing cell lines with xenoAgs green fluorescent protein and firefly luciferase was elucidated using flow cytometry, ELISA, and ELISpot assays. Results In our model, leukemia responsiveness correlates with in vivo CD4+ T cell activation and DC maturation, supporting a role for DC licensing. In contrast, tolerance is characterized by in vivo increased expression of negative immune checkpoints (IC) which may suppress rather than license DC. In vitro assays confirm the ability of CD4+ T cells from leukemia‐responsive mice to promote robust maturation of naïve bone marrow DC in the presence of non‐immunogenic leukemia antigens. Conclusion Together these findings support a CD4+ T cell‐mediated mechanism of DC licensing to promote multi‐Ag immune responses that may augment current targeted immunotherapies and avoid relapses in treated children with ALL. |
| format | Article |
| id | doaj-art-b24f63a26ce44cd6bd047b1a51a80357 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-b24f63a26ce44cd6bd047b1a51a803572025-01-13T13:22:38ZengWileyCancer Medicine2045-76342025-01-01141n/an/a10.1002/cam4.70508CD4+ T Cells Mediate Dendritic Cell Licensing to Promote Multi‐Antigen Anti‐Leukemic Immune ResponseLuis Gil‐de‐Gómez0Joseph J. Mattei1Jessica H. Lee2Stephan A. Grupp3Gregor S. D. Reid4Alix E. Seif5Division of Oncology The Children's Hospitial of Philadelphia Philadelphia Pennsylvania USADivision of Oncology The Children's Hospitial of Philadelphia Philadelphia Pennsylvania USADivision of Oncology The Children's Hospitial of Philadelphia Philadelphia Pennsylvania USADivision of Oncology The Children's Hospitial of Philadelphia Philadelphia Pennsylvania USAMichael Cuccione Childhood Cancer Research Program BC Children's Hospital Research Institute Vancouver British Columbia CanadaDivision of Oncology The Children's Hospitial of Philadelphia Philadelphia Pennsylvania USAABSTRACT Background Single antigen (Ag)‐targeted immunotherapies for acute lymphoblastic leukemia (ALL) are highly effective; however, up to 50% of patients relapse after these treatments. Most of these relapses lack target Ag expression, suggesting targeting multiple Ags would be advantageous. Materials & Methods The multi‐Ag immune responses to ALL induced by transducing cell lines with xenoAgs green fluorescent protein and firefly luciferase was elucidated using flow cytometry, ELISA, and ELISpot assays. Results In our model, leukemia responsiveness correlates with in vivo CD4+ T cell activation and DC maturation, supporting a role for DC licensing. In contrast, tolerance is characterized by in vivo increased expression of negative immune checkpoints (IC) which may suppress rather than license DC. In vitro assays confirm the ability of CD4+ T cells from leukemia‐responsive mice to promote robust maturation of naïve bone marrow DC in the presence of non‐immunogenic leukemia antigens. Conclusion Together these findings support a CD4+ T cell‐mediated mechanism of DC licensing to promote multi‐Ag immune responses that may augment current targeted immunotherapies and avoid relapses in treated children with ALL.https://doi.org/10.1002/cam4.70508acute lymphoblastic leukemiaCD4+ T cellsdendritic cellsNeoantigens |
| spellingShingle | Luis Gil‐de‐Gómez Joseph J. Mattei Jessica H. Lee Stephan A. Grupp Gregor S. D. Reid Alix E. Seif CD4+ T Cells Mediate Dendritic Cell Licensing to Promote Multi‐Antigen Anti‐Leukemic Immune Response Cancer Medicine acute lymphoblastic leukemia CD4+ T cells dendritic cells Neoantigens |
| title | CD4+ T Cells Mediate Dendritic Cell Licensing to Promote Multi‐Antigen Anti‐Leukemic Immune Response |
| title_full | CD4+ T Cells Mediate Dendritic Cell Licensing to Promote Multi‐Antigen Anti‐Leukemic Immune Response |
| title_fullStr | CD4+ T Cells Mediate Dendritic Cell Licensing to Promote Multi‐Antigen Anti‐Leukemic Immune Response |
| title_full_unstemmed | CD4+ T Cells Mediate Dendritic Cell Licensing to Promote Multi‐Antigen Anti‐Leukemic Immune Response |
| title_short | CD4+ T Cells Mediate Dendritic Cell Licensing to Promote Multi‐Antigen Anti‐Leukemic Immune Response |
| title_sort | cd4 t cells mediate dendritic cell licensing to promote multi antigen anti leukemic immune response |
| topic | acute lymphoblastic leukemia CD4+ T cells dendritic cells Neoantigens |
| url | https://doi.org/10.1002/cam4.70508 |
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