Both T cell priming in lymph node and CXCR3-dependent migration are the key events for predicting the response of atezolizumab.
Sci Rep
; 11(1): 13912, 2021 07 06.
Article
en En
| MEDLINE
| ID: mdl-34230534
ABSTRACT
Anti-PD-L1 antibodies benefit many cancer patients, even those with "non-inflamed tumor". Determining which patients will benefit remains an important clinical goal. In a non-inflamed tumor mouse model, we found that PD-L1 was highly expressed on antigen-presenting cells (APCs) especially on CD103+ CD11c+ dendritic cells in tumor-draining lymph nodes (dLNs), suppressing T-cell priming by APCs. In this model, anti-PD-L1 antibodies enhanced T-cell priming and increased CXCR3+ activated T-cells in dLNs, which was followed by the trafficking of T-cells to tumors in response to CXCR3 ligands. As predictive biomarker, each APCs-related gene expression (AP score) alone or T-cells trafficking-related chemokine gene expression (T score) alone were still less than perfect among the 17 mouse models examined. However a combining score of AP score and T score (AP/T score) precisely identified anti-PD-L1-sensitive tumors. In the phase 3 trial of atezolizumab vs docetaxel in advanced NSCLC patients (OAK), the AP/T score could identify atezolizumab-treated NSCLC patients who achieved significant improvement in overall survival. This biomarker concept would be a clinically valuable for prediction of anti-PD-L1 antibody efficacy.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T
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Movimiento Celular
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Reactividad Cruzada
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Receptores CXCR3
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Anticuerpos Monoclonales Humanizados
/
Ganglios Linfáticos
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article