Copy Neutral LOH Affecting the Entire Chromosome 6 Is a Frequent Mechanism of HLA Class I Alterations in Cancer
Metadatos
Afficher la notice complèteAuteur
Garrido, María Antonia; Ruiz-Cabello Osuna, Francisco; Garrido Torres-Puchol, Federico; Aptsiauri, NataliaEditorial
MDPI
Materia
Cancer immune escape HLA class I Copy-neutral loss of heterozygosity (CN-LOH) Antigen presentation Beta2-microglobulin Cytotoxic T-cells Cancer immunotherapy
Date
2021Referencia bibliográfica
Garrido, M.A.; Perea, F.; Vilchez, J.R.; Rodríguez, T.; Anderson, P.; Garrido, F.; Ruiz-Cabello, F.; Aptsiauri, N. Copy Neutral LOH Affecting the Entire Chromosome 6 Is a Frequent Mechanism of HLA Class I Alterations in Cancer. Cancers 2021, 13, 5046. https://doi.org/10.3390/ cancers13205046
Patrocinador
ISCIII Research Institute co-financed by the European Union and Ministerio de Ciencia e Innovación (FEDER-Fondo Europeo de Desarrollo Regional and National Plan 2020, MICIN) (PI17/00197, PI18/00826, and PID2020-115087GB-100); Junta de Andalucía in Spain (Group CTS-143 and B-CTS-410-UGR-20); Consejería de Salud, Junta de Andalucía through the contract “Nicolás Monardes” [C-0013-2018]Résumé
Total or partial loss of HLA class I antigens reduce the recognition of specific tumor peptides
by cytotoxic T lymphocytes favoring cancer immune escape during natural tumor evolution. These
alterations can be caused by genomic defects, such as loss of heterozygosity at chromosomes 6 and 15
(LOH-6 and LOH-15), where HLA class I genes are located. There is growing evidence indicating that
LOH in HLA contributes to the immune selection of HLA loss variants and influences the resistance
to immunotherapy. Nevertheless, the incidence and the mechanism of this chromosomal aberration
involving HLA genes has not been systematically assessed in different types of tumors and often
remains underestimated. Here, we used SNP arrays to investigate the incidence and patterns of
LOH-6 and LOH-15 in a number of human cancer cell lines and tissues of different histological types.
We observed that LOH in HLA is a common event in cancer samples with a prevalence of a copy
neutral type of LOH (CN-LOH) that affects entire chromosome 6 or 15 and involves chromosomal
duplications. LOH-6 was observed more often and was associated with homozygous HLA genotype
and partial HLA loss of expression. We also discuss the immunologic and clinical implications of
LOH in HLA on tumor clonal expansion and association with the cancer recurrence after treatment.