Therapeutic melanoma vaccine with cancer stem cell phenotype represses exhaustion and maintains antigen-specific T cell stemness by up-regulating BCL6.
BCL6
Genetically-modified whole cell melanoma vaccine
Melanoma
Microarray
Transcriptome profile
Journal
Oncoimmunology
ISSN: 2162-4011
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
2020
2020
Historique:
received:
23
05
2019
revised:
08
11
2019
accepted:
13
11
2019
entrez:
1
2
2020
pubmed:
1
2
2020
medline:
1
2
2020
Statut:
epublish
Résumé
We developed a therapeutic, gene-modified, allogeneic melanoma vaccine (AGI-101H), which, upon genetic modification, acquired melanoma stem cell-like phenotype. Since its initial clinical trial in 1997, the vaccine has resulted in the long-term survival of a substantial fraction of immunized patients (up to 20 years). Here, we investigated the potential molecular mechanisms underlying the long-lasting effect of AGI-101H using transcriptome profiling of patients' peripheral T lymphocytes. Magnetically-separated T lymphocytes from AGI-101H-immunized long-term survivors, untreated melanoma patients, and healthy controls were subjected to transcriptome profiling using the microarray analyses. Data were analyzed with a multitude of bioinformatics tools (WebGestalt, DAVID, GSEA) and the results were validated with RT-qPCR. We found substantial differences in the transcriptomes of healthy controls and melanoma patients (both untreated and AGI-101H-vaccinated). AGI-101H immunization induced similar profiles of peripheral T cells as tumor residing in untreated patients. This suggests that whole stem cells immunization mobilizes analogous peripheral T cells to the natural adaptive anti-melanoma response. Moreover, AGI-101H treatment activated the TNF-α and TGF-β signaling pathways and dampened IL2-STAT5 signaling in T cells, which finally resulted in the significant up-regulation of a
Identifiants
pubmed: 32002306
doi: 10.1080/2162402X.2019.1710063
pii: 1710063
pmc: PMC6959432
doi:
Substances chimiques
BCL6 protein, human
0
Cancer Vaccines
0
Proto-Oncogene Proteins c-bcl-6
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
1710063Informations de copyright
© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
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