ADA/CD26 axis increases intra-tumor PD-1+CD28+CD8+ T-cell fitness and affects NSCLC prognosis and response to ICB.
Oncoimmunology
; 13(1): 2371051, 2024.
Article
en En
| MEDLINE
| ID: mdl-38915783
ABSTRACT
Improving cancer immunotherapy efficacy hinges on identifying key T-cell populations critical for tumor control and response to Immune Checkpoint Blockade (ICB). We have recently reported that while the co-expression of PD-1 and CD28 is associated with impaired functionality in peripheral blood, it significantly enhances T-cell fitness in the tumor site of non-small cell lung cancer (NSCLC) patients. To uncover the underlying mechanisms, we explored the role of CD26, a key player in T-cell activation through its interaction with adenosine deaminase (ADA), a crucial intra/extracellular enzyme able to neutralize local adenosine (ADO). We found that an autocrine ADA/CD26 axis enhances CD8+PD-1+CD28+ T-cell function, particularly within an immunosuppressive environment marked by CD39 expression. Then, we interrogated the TCGA and OAK datasets to gain insight into the prognostic/predictive potential of our findings. We identified a signature predicting overall survival (OS) in LUAD patients and response to atezolizumab in advanced LUAD cases. These findings suggest promising avenues for therapeutic intervention targeting the ADA/CD26 axis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Adenosina Desaminasa
/
Antígenos CD28
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Carcinoma de Pulmón de Células no Pequeñas
/
Linfocitos T CD8-positivos
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Dipeptidil Peptidasa 4
/
Receptor de Muerte Celular Programada 1
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Inhibidores de Puntos de Control Inmunológico
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Neoplasias Pulmonares
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Oncoimmunology
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia