Boyero, LauraSánchez-Gastaldo, AmparoAlonso, MiriamNoguera-Uclés, José FranciscoMolina-Pinelo, SoniaBernabé-Caro, Reyes2022-06-032022-06-032020-12-11Boyero 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):3729http://hdl.handle.net/10668/3672After 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Lung cancerImmunotherapyResistance mechanismsPD-1/PD-L1Immune checkpoint inhibitorsMonoclonal antibodiesNSCLCSCLCNeoplasias pulmonaresInmunoterapiaReceptor de muerte celular programada 1Antígeno B7-H1Inhibidores de puntos de control inmunológicoAnticuerpos monoclonalesCarcinoma de pulmón de células no pequeñasCarcinoma pulmonar de células pequeñasMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Quality of LifeMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cellular Microenvironment::Tumor MicroenvironmentMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::ImmunotherapyMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung NeoplasmsMedical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-LymphocytesMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal TransductionMedical Subject Headings::Phenomena and Processes::Microbiological Phenomena::MicrobiotaMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, GeneticMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrencereview article33322522open access10.3390/cancers121237292072-6694PMC7763130