The Resistance Mechanisms of Checkpoint Inhibitors in Solid Tumors. 2020

Evangelos Koustas, and Panagiotis Sarantis, and Athanasios G Papavassiliou, and Michalis V Karamouzis
Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.

The emergence of cancer immunotherapy has already shown some remarkable results, having changed the treatment strategy in clinical practice for solid tumors. Despite these promising long-term responses, patients seem to lack the ability to respond to immune checkpoint inhibitors, thus demonstrating a primary resistance to immunotherapy. Moreover, a significant number of patients who initially respond to treatment eventually acquire resistance to immunotherapy. Both resistance mechanisms are a result of a complex interaction among different molecules, pathways, and cellular processes. Several resistance mechanisms, such as tumor microenvironment modification, autophagy, genetic and epigenetic alterations, tumor mutational burden, neo-antigens, and modulation of gut microbiota have already been identified, while more continue to be uncovered. In this review, we discuss the latest milestones in the field of immunotherapy, resistance mechanisms against this type of therapy as well as putative therapeutic strategies to overcome resistance in solid tumors.

UI MeSH Term Description Entries
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000082082 Immune Checkpoint Inhibitors Drugs that block negative regulator IMMUNE CHECKPOINT proteins (e.g., PD-1 RECEPTOR and CTLA-4 ANTIGEN) thereby increasing suppressed immune activation in immunotherapies. CTLA-4 Inhibitor,CTLA-4 Inhibitors,Cytotoxic T-Lymphocyte-Associated Protein 4 Inhibitor,Cytotoxic T-Lymphocyte-Associated Protein 4 Inhibitors,Immune Checkpoint Blockade,Immune Checkpoint Blockers,Immune Checkpoint Inhibition,Immune Checkpoint Inhibitor,PD-1 Inhibitor,PD-1 Inhibitors,PD-1-PD-L1 Blockade,PD-L1 Inhibitor,PD-L1 Inhibitors,Programmed Cell Death Protein 1 Inhibitor,Programmed Cell Death Protein 1 Inhibitors,Programmed Death-Ligand 1 Inhibitors,Blockade, PD-1-PD-L1,CTLA 4 Inhibitor,CTLA 4 Inhibitors,Checkpoint Blockade, Immune,Checkpoint Blockers, Immune,Checkpoint Inhibition, Immune,Checkpoint Inhibitor, Immune,Checkpoint Inhibitors, Immune,Cytotoxic T Lymphocyte Associated Protein 4 Inhibitor,Cytotoxic T Lymphocyte Associated Protein 4 Inhibitors,Inhibitor, PD-1,PD 1 Inhibitor,PD 1 Inhibitors,PD 1 PD L1 Blockade,PD L1 Inhibitor,PD L1 Inhibitors,Programmed Death Ligand 1 Inhibitors
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D019008 Drug Resistance, Neoplasm Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures. Antibiotic Resistance, Neoplasm,Antineoplastic Drug Resistance,Drug Resistance, Antineoplastic,Antineoplastic Agent Resistance,Neoplasm Drug Resistance,Resistance, Antineoplastic Agent,Resistance, Antineoplastic Drug

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