CD28/PD1 co-expression: dual impact on CD8
CD28
CD8+ T cells
Immune Checkpoint Blockade
Non-small cell lung cancer
PD-1
Single-cell RNA-Seq
T-cell functionality
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
28 Oct 2023
28 Oct 2023
Historique:
received:
27
07
2023
accepted:
29
09
2023
medline:
30
10
2023
pubmed:
29
10
2023
entrez:
29
10
2023
Statut:
epublish
Résumé
Immune checkpoint blockade (ICB) has significantly prolonged survival of non-small cell lung cancer (NSCLC) patients, although most patients develop mechanisms of resistance. Recently single-cell RNA-sequencing (scRNA-Seq) revealed a huge T-cell phenotypic and (dys)functional state variability. Accordingly, T-cell exhaustion is recognized as a functional adaptation, with a dynamic progression from a long-lived "pre-exhausted stem-like progenitor" to a "terminally exhausted" state. In this scenario it is crucial to understand the complex interplay between co-stimulatory and inhibitory molecules in CD8 To gain a baseline landscape of the composition, functional states, and transcriptomic signatures predictive of prognosis, we analyzed CD8 Despite the increased PD1 levels, an improved PD1 Our findings identify signatures able to stratify survival of LUAD patients and predict ICB response in advanced NSCLC. CD28 is advocated as a key determinant in the signatures identified, in both periphery and tumor site, thus likely providing feasible biomarkers of ICB response.
Sections du résumé
BACKGROUND
BACKGROUND
Immune checkpoint blockade (ICB) has significantly prolonged survival of non-small cell lung cancer (NSCLC) patients, although most patients develop mechanisms of resistance. Recently single-cell RNA-sequencing (scRNA-Seq) revealed a huge T-cell phenotypic and (dys)functional state variability. Accordingly, T-cell exhaustion is recognized as a functional adaptation, with a dynamic progression from a long-lived "pre-exhausted stem-like progenitor" to a "terminally exhausted" state. In this scenario it is crucial to understand the complex interplay between co-stimulatory and inhibitory molecules in CD8
METHODS
METHODS
To gain a baseline landscape of the composition, functional states, and transcriptomic signatures predictive of prognosis, we analyzed CD8
RESULTS
RESULTS
Despite the increased PD1 levels, an improved PD1
CONCLUSIONS
CONCLUSIONS
Our findings identify signatures able to stratify survival of LUAD patients and predict ICB response in advanced NSCLC. CD28 is advocated as a key determinant in the signatures identified, in both periphery and tumor site, thus likely providing feasible biomarkers of ICB response.
Identifiants
pubmed: 37898752
doi: 10.1186/s13046-023-02846-3
pii: 10.1186/s13046-023-02846-3
pmc: PMC10612243
doi:
Substances chimiques
CD28 Antigens
0
Immune Checkpoint Inhibitors
0
Hepatitis A Virus Cellular Receptor 2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
287Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG 19822
Organisme : Ministero della Salute
ID : Ricerca corrente 2023
Informations de copyright
© 2023. The Author(s).
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