BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti-PD-1/PD-L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity.
Adv Sci (Weinh)
; 10(8): e2207155, 2023 03.
Article
en En
| MEDLINE
| ID: mdl-36642843
ABSTRACT
To improve response rate of monotherapy of immune checkpoint blockade (ICB), it is necessary to find an emerging target in combination therapy. Through analyzing tumor microenvironment (TME)-related indicators, it is validated that BCAT2 shapes a noninflamed TME in bladder cancer. The outcomes of multiomics indicate that BCAT2 has an inhibitory effect on cytotoxic lymphocyte recruitment by restraining activities of proinflammatory cytokine/chemokine-related pathways and T-cell-chemotaxis pathway. Immunoassays reveal that secretion of CD8+ T-cell-related chemokines keeps a robust negative correlation with BCAT2, generating a decreasing tendency of CD8+ T cells around BCAT2+ tumor cells from far to near. Cotreatment of BCAT2 deficiency and anti-PD-1 antibody has a synergistic effect in vivo, implying the potential of BCAT2 in combination therapy. Moreover, the value of BCAT2 in predicting efficacy of immunotherapy is validated in multiple immunotherapy cohorts. Together, as a key molecule in TME, BCAT2 is an emerging target in combination with ICB and a biomarker of guiding precision therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Microambiente Tumoral
/
Antígeno B7-H1
/
Inhibidores de Puntos de Control Inmunológico
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Inmunoterapia
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Adv Sci (Weinh)
Año:
2023
Tipo del documento:
Article