Role of Human Leukocyte Antigen System as A Predictive Biomarker for Checkpoint-Based Immunotherapy in Cancer Patients.
biomarker
cancer immunotherapy
carcinogenesis
major histocompatibility complex (MHC), human leukocyte antigen (HLA), antigen processing machinery (APM) molecules
tumor predisposition
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
02 Oct 2020
02 Oct 2020
Historique:
received:
20
08
2020
revised:
26
09
2020
accepted:
29
09
2020
entrez:
7
10
2020
pubmed:
8
10
2020
medline:
27
2
2021
Statut:
epublish
Résumé
Recent advances in cancer immunotherapy have clearly shown that checkpoint-based immunotherapy is effective in a small subgroup of cancer patients. However, no effective predictive biomarker has been identified so far. The major histocompatibility complex, better known in humans as human leukocyte antigen (HLA), is a very polymorphic gene complex consisting of more than 200 genes. It has a crucial role in activating an appropriate host immune response against pathogens and tumor cells by discriminating self and non-self peptides. Several lines of evidence have shown that down-regulation of expression of HLA class I antigen derived peptide complexes by cancer cells is a mechanism of tumor immune escape and is often associated to poor prognosis in cancer patients. In addition, it has also been shown that HLA class I and II antigen expression, as well as defects in the antigen processing machinery complex, may predict tumor responses in cancer immunotherapy. Nevertheless, the role of HLA in predicting tumor responses to checkpoint-based immunotherapy is still debated. In this review, firstly, we will describe the structure and function of the HLA system. Secondly, we will summarize the HLA defects and their clinical significance in cancer patients. Thirdly, we will review the potential role of the HLA as a predictive biomarker for checkpoint-based immunotherapy in cancer patients. Lastly, we will discuss the potential strategies that may restore HLA function to implement novel therapeutic strategies in cancer patients.
Identifiants
pubmed: 33023239
pii: ijms21197295
doi: 10.3390/ijms21197295
pmc: PMC7582904
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
HLA Antigens
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : 2017PHRC8X_003
Organisme : Fondazione CON IL SUD
ID : Brains2South 2015 PDR-0224
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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