Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond
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 va...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.944872/full |
| _version_ | 1828229460193705984 |
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| author | Simona Pagliuca Simona Pagliuca Carmelo Gurnari Carmelo Gurnari Marie Thérèse Rubio Valeria Visconte Tobias L. Lenz |
| author_facet | Simona Pagliuca Simona Pagliuca Carmelo Gurnari Carmelo Gurnari Marie Thérèse Rubio Valeria Visconte Tobias L. Lenz |
| author_sort | Simona Pagliuca |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T18:35:21Z |
| format | Article |
| id | doaj.art-e8786f73237f4b80b78ec70a9166d751 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T18:35:21Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e8786f73237f4b80b78ec70a9166d7512022-12-22T03:20:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.944872944872Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyondSimona Pagliuca0Simona Pagliuca1Carmelo Gurnari2Carmelo Gurnari3Marie Thérèse Rubio4Valeria Visconte5Tobias L. Lenz6Translational Hematology and Oncology Research Department, Cleveland Clinic, Cleveland, OH, United StatesService d’hématologie Clinique, Hôpital Brabois, CHRU Nancy and CNRS UMR 7365 IMoPa, Biopole de l’Université de Loarraine, Vandoeuvre les Nancy, FranceTranslational Hematology and Oncology Research Department, Cleveland Clinic, Cleveland, OH, United StatesDepartment of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, ItalyService d’hématologie Clinique, Hôpital Brabois, CHRU Nancy and CNRS UMR 7365 IMoPa, Biopole de l’Université de Loarraine, Vandoeuvre les Nancy, FranceTranslational Hematology and Oncology Research Department, Cleveland Clinic, Cleveland, OH, United StatesResearch Unit for Evolutionary Immunogenomics, Department of Biology, University of Hamburg, Hamburg, GermanyStructural 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.944872/fullHLAimmunopeptidomeHLA evolutionary divergencetumor surveillanceimmune escape |
| spellingShingle | Simona Pagliuca Simona Pagliuca Carmelo Gurnari Carmelo Gurnari Marie Thérèse Rubio Valeria Visconte Tobias L. Lenz Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond Frontiers in Immunology HLA immunopeptidome HLA evolutionary divergence tumor surveillance immune escape |
| title | Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond |
| title_full | Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond |
| title_fullStr | Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond |
| title_full_unstemmed | Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond |
| title_short | Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond |
| title_sort | individual hla heterogeneity and its implications for cellular immune evasion in cancer and beyond |
| topic | HLA immunopeptidome HLA evolutionary divergence tumor surveillance immune escape |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.944872/full |
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