Beyond the Barrier: Unraveling the Mechanisms of Immunotherapy Resistance.
Annu Rev Immunol
; 42(1): 521-550, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38382538
ABSTRACT
Immune checkpoint blockade (ICB) induces a remarkable and durable response in a subset of cancer patients. However, most patients exhibit either primary or acquired resistance to ICB. This resistance arises from a complex interplay of diverse dynamic mechanisms within the tumor microenvironment (TME). These mechanisms include genetic, epigenetic, and metabolic alterations that prevent T cell trafficking to the tumor site, induce immune cell dysfunction, interfere with antigen presentation, drive heightened expression of coinhibitory molecules, and promote tumor survival after immune attack. The TME worsens ICB resistance through the formation of immunosuppressive networks via immune inhibition, regulatory metabolites, and abnormal resource consumption. Finally, patient lifestyle factors, including obesity and microbiome composition, influence ICB resistance. Understanding the heterogeneity of cellular, molecular, and environmental factors contributing to ICB resistance is crucial to develop targeted therapeutic interventions that enhance the clinical response. This comprehensive overview highlights key mechanisms of ICB resistance that may be clinically translatable.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Resistencia a Antineoplásicos
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Microambiente Tumoral
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Inhibidores de Puntos de Control Inmunológico
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Inmunoterapia
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Neoplasias
Idioma:
En
Revista:
Annu Rev Immunol
Año:
2024
Tipo del documento:
Article