CD4 Phenotypes Are Associated with Reduced Expansion of Tumor-Infiltrating Lymphocytes in Melanoma Patients Treated with Adoptive Cell Therapy.
Journal
Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R
Informations de publication
Date de publication:
01 09 2023
01 09 2023
Historique:
received:
07
04
2023
accepted:
04
07
2023
pmc-release:
01
09
2024
medline:
23
8
2023
pubmed:
19
7
2023
entrez:
19
7
2023
Statut:
ppublish
Résumé
Tumor-infiltrating lymphocyte (TIL) adoptive cell therapy is effective in treating malignant melanoma, but its success relies on the adequate ex vivo expansion of TIL. To assess correlates of TIL expansion, CD4+ and CD8+ TIL were analyzed by RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing of acetylated histone 3. Patients were grouped into "TIL high" and "TIL low" based on division at the median number of TIL infused. Greater numbers of TIL infused correlated with longer overall survival, and increased frequencies of CD4+ cells infused were negatively correlated with the number of TIL infused. RNA-seq analysis of CD4+ TIL showed increases in Th2/Th17/regulatory T cell-related transcripts and pathways in the TIL-low group. Analysis of a public single-cell RNA-seq dataset validated findings that increased frequencies of CD4+ cells were negatively correlated with the number of TIL infused. TIL-low patients had significantly increased frequencies of CD4+ cells expressing ETS2 and OSM and trended toward increased expression of TNFRSF18.
Identifiants
pubmed: 37466381
pii: 265783
doi: 10.4049/jimmunol.2300250
pmc: PMC10528290
mid: NIHMS1915816
doi:
Substances chimiques
Interleukin-2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
735-742Subventions
Organisme : NCI NIH HHS
ID : R00 CA230201
Pays : United States
Informations de copyright
Copyright © 2023 by The American Association of Immunologists, Inc.
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