Immune checkpoints and cancer in the immunogenomics era

• Published in: Briefings in functional genomics Vol. 18; no. 2; pp. 133 - 139
• Main Authors: Park, Ryan, Winnicki, Mary, Liu, Evan, Chu, Wen-Ming
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 22.03.2019
• Subjects: antigens; Food and Drug Administration; genomics; immunotherapy; melanoma; nucleic acids; immunogenomics; neoantigen; mutation; PD-L1; CTLA-4; somatic; resistance to checkpoint blockade; PD-1; MMR deficiency; immune checkpoint blockade; POLE
• ISSN: 2041-2657; 2041-2649; 2041-2657
• DOI: 10.1093/bfgp/ely027

Abstract Immune checkpoints have been the subject of a wave of new studies. Among these checkpoints are tytotoxic T-lymphocyte-associated antigen 4, checkpoints programmed death-1 and programmed death-ligand 1; their blockades have been approved by the Food and Drug Administration for therapy of melanoma and other types of cancers. Immunogenomics, which combines the latest nucleic acid sequencing strategy with immunotherapy, provides precise information about genomic alterations (e.g. mutations) and enables a paradigm shift of immune checkpoint therapy from tumor types to molecular signatures. Studying these critical checkpoints in relation to genomic mutations and neoantigens has produced groundbreaking results. This article examines these studies and delves into the relationships between immune checkpoint blockade and tumors harboring certain genomic mutations. Moreover, this article reviews recent studies on resistance to immune checkpoint therapy.