Structural and functional variability of human leukocyte antigen (HLA) is the foundation for competent adaptive immune responses against pathogen and tumor antigens as it assures the breadth of the presented immune-peptidome, theoretically sustaining an efficient and diverse T cell response. This variability is presumably the result of the continuous selection by pathogens, which over the course of evolution shaped the adaptive immune system favoring the assortment of a hyper-polymorphic HLA system able to elaborate efficient immune responses. Any genetic alteration affecting this diversity may lead to pathological processes, perturbing antigen presentation capabilities, T-cell reactivity and, to some extent, natural killer cell functionality. A highly variable germline HLA genotype can convey immunogenetic protection against infections, be associated with tumor surveillance or influence response to anti-neoplastic treatments. In contrast, somatic aberrations of HLA loci, rearranging the original germline configuration, theoretically decreasing its variability, can facilitate mechanisms of immune escape that promote tumor growth and immune resistance.The purpose of the present review is to provide a unified and up-to-date overview of the pathophysiological consequences related to the perturbations of the genomic heterogeneity of HLA complexes and their impact on human diseases, with a special focus on cancer.

Pagliuca, S., Gurnari, C., Rubio, M.t., Visconte, V., Lenz, T.l. (2022). Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond. FRONTIERS IN IMMUNOLOGY, 13, 1-11 [10.3389/fimmu.2022.944872].

Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond

Gurnari, Carmelo
Writing – Review & Editing
;
2022-01-01

Abstract

Structural and functional variability of human leukocyte antigen (HLA) is the foundation for competent adaptive immune responses against pathogen and tumor antigens as it assures the breadth of the presented immune-peptidome, theoretically sustaining an efficient and diverse T cell response. This variability is presumably the result of the continuous selection by pathogens, which over the course of evolution shaped the adaptive immune system favoring the assortment of a hyper-polymorphic HLA system able to elaborate efficient immune responses. Any genetic alteration affecting this diversity may lead to pathological processes, perturbing antigen presentation capabilities, T-cell reactivity and, to some extent, natural killer cell functionality. A highly variable germline HLA genotype can convey immunogenetic protection against infections, be associated with tumor surveillance or influence response to anti-neoplastic treatments. In contrast, somatic aberrations of HLA loci, rearranging the original germline configuration, theoretically decreasing its variability, can facilitate mechanisms of immune escape that promote tumor growth and immune resistance.The purpose of the present review is to provide a unified and up-to-date overview of the pathophysiological consequences related to the perturbations of the genomic heterogeneity of HLA complexes and their impact on human diseases, with a special focus on cancer.
2022
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - MALATTIE DEL SANGUE
English
HLA
HLA evolutionary divergence
immune escape
immunopeptidome
tumor surveillance
Pagliuca, S., Gurnari, C., Rubio, M.t., Visconte, V., Lenz, T.l. (2022). Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond. FRONTIERS IN IMMUNOLOGY, 13, 1-11 [10.3389/fimmu.2022.944872].
Pagliuca, S; Gurnari, C; Rubio, Mt; Visconte, V; Lenz, Tl
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/311860
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