RT Journal Article T1 Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy A1 Boyero, Laura A1 Sánchez-Gastaldo, Amparo A1 Alonso, Miriam A1 Noguera-Uclés, José Francisco A1 Molina-Pinelo, Sonia A1 Bernabé-Caro, Reyes K1 Lung cancer K1 Immunotherapy K1 Resistance mechanisms K1 PD-1/PD-L1 K1 Immune checkpoint inhibitors K1 Monoclonal antibodies K1 NSCLC K1 SCLC K1 Neoplasias pulmonares K1 Inmunoterapia K1 Receptor de muerte celular programada 1 K1 Antígeno B7-H1 K1 Inhibidores de puntos de control inmunológico K1 Anticuerpos monoclonales K1 Carcinoma de pulmón de células no pequeñas K1 Carcinoma pulmonar de células pequeñas AB 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. PB MDPI YR 2020 FD 2020-12-11 LK http://hdl.handle.net/10668/3672 UL http://hdl.handle.net/10668/3672 LA en NO Boyero L, Sánchez-Gastaldo A, Alonso M, Noguera-Uclés JF, Molina-Pinelo S, Bernabé-Caro R. Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy. Cancers. 2020 Dec 11;12(12):3729 DS RISalud RD Apr 11, 2025