Primary and acquired resistance to immunotherapy in lung cancer: unveiling the mechanisms underlying of immune checkpoint blockade therapy

After several decades without maintained responses or long-term survival of patients with lung cancer, novel therapies have emerged as a hopeful milestone in this research field. The appearance of immunotherapy, especially immune checkpoint inhibitors, has improved both the overall survival and qual...

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Detalles Bibliográficos
Autores: Boyero, Laura, Sanchez-Gastaldo, Amparo, Alonso, Miriam, Noguera Uclés, José Francisco, Molina Pinelo, Sonia, Bernabé-Caro, Reyes
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/104941
Acceso en línea:https://hdl.handle.net/11441/104941
https://doi.org/10.3390/cancers12123729
Access Level:acceso abierto
Palabra clave:lung cancer
Immunotherapy
Resistance mechanisms
PD-1/PD-L1
Immune checkpoint inhibitors
Monoclonal antibodies
NSCLC
SCLC
Descripción
Sumario:After several decades without maintained responses or long-term survival of patients with lung cancer, novel therapies have emerged as a hopeful milestone in this research field. The appearance of immunotherapy, especially immune checkpoint inhibitors, has improved both the overall survival and quality of life of patients, many of whom are diagnosed late when classical treatments are ineffective. Despite these unprecedented results, a high percentage of patients do not respond initially to treatment or relapse after a period of response. This is due to resistance mechanisms, which require understanding in order to prevent them and develop strategies to overcome them and increase the number of patients who can benefit from immunotherapy. This review highlights the current knowledge of the mechanisms and their involvement in resistance to immunotherapy in lung cancer, such as aberrations in tumor neoantigen burden, effector T-cell infiltration in the tumor microenvironment (TME), epigenetic modulation, the transcriptional signature, signaling pathways, T-cell exhaustion, and the microbiome. Further research dissecting intratumor and host heterogeneity is necessary to provide answers regarding the immunotherapy response and develop more effective treatments for lung cancer.