A Newly Licensed Peptide Presenter HLA-F: the Occurrence and the Prognostic Significance of this Cancer Immunoediting Molecule in Renal Cell Carcinoma and its Occurrence in Glioblastoma

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F18%3A00069189" target="_blank" >RIV/65269705:_____/18:00069189 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/labinvest201820" target="_blank" >https://www.nature.com/articles/labinvest201820</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/labinvest.2018.20" target="_blank" >10.1038/labinvest.2018.20</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A Newly Licensed Peptide Presenter HLA-F: the Occurrence and the Prognostic Significance of this Cancer Immunoediting Molecule in Renal Cell Carcinoma and its Occurrence in Glioblastoma

Popis výsledku v původním jazyce

Among cancer immonoediting non-classical human leucocyte antigens (HLA) class Ib, HLA-F remains to be the most enigmatic. Originally it was thought to be specifically expressed only by extravillous trophoblast, which indicated its physiological role in a development of maternal tolerance to a semiallogeneic fetus (via engagement with inhibitory receptors on NK cells, mechanism also adopted by cancer cells to bypass host immunity). The expression by trophoblast was recently confirmed (Hackmon R 2017). Moreover, recently a peptide presenting function (presentation of peptides of unconventional length) was described in HLA-F (Dulberger CL 2017). Renal cell carcinoma (RCC) is characterized by its immunogenicity. Glioblastoma (GB) is a malignancy of an immune privileged site. An expression and prognostic significance of HLA-F by neoplastic cells in RCC and the expression in GB is not characterized. We evaluated the expression of HLA-F specific mRNA transcripts produced by neoplastic cells in 73 cases of RCC and in 54 samples of normal kidney parenchyma. We also evaluated expression of HLA-F molecule immunohistochemically in a pilot study of 24 cases of GB (IDH-wildtype in accordance with WHO 2016 revision). The results in RCC were statistically correlated with several clinicopathological parameters. We revealed that HLA-F is up-regulated in RCC (Tab.). On the other hand, its up-regulation is counterintuitively associated with prolonged disease-free survival (Fig. 1), more favorable pT stage and lower nuclear Fuhrmann&apos;s grade. In the pilot study of GB, we found cytoplasmic expression of HLA-F (Fig. 2) in 10 cases (42%). Because of a possibility of aberrant activation of expression of non-classical HLA molecules by interferons, the identification of HLA-F status could contribute to better selection of patients with RCC who could possibly benefit from more tailored neoadjuvant biological/immunological therapy. This molecule could represent useful prognostic biomarker in RCC. Non-classical molecule HLA-F, recently proven to be a peptide presenter, physiologically protects the fetus from maternal allorecognition. Our results suggest its role in cancer immunoediting in RCC and we proved its cytopasmic expression in 42% of cases of GB. Further studies appear warrantied.

Název v anglickém jazyce

A Newly Licensed Peptide Presenter HLA-F: the Occurrence and the Prognostic Significance of this Cancer Immunoediting Molecule in Renal Cell Carcinoma and its Occurrence in Glioblastoma

Popis výsledku anglicky

Among cancer immonoediting non-classical human leucocyte antigens (HLA) class Ib, HLA-F remains to be the most enigmatic. Originally it was thought to be specifically expressed only by extravillous trophoblast, which indicated its physiological role in a development of maternal tolerance to a semiallogeneic fetus (via engagement with inhibitory receptors on NK cells, mechanism also adopted by cancer cells to bypass host immunity). The expression by trophoblast was recently confirmed (Hackmon R 2017). Moreover, recently a peptide presenting function (presentation of peptides of unconventional length) was described in HLA-F (Dulberger CL 2017). Renal cell carcinoma (RCC) is characterized by its immunogenicity. Glioblastoma (GB) is a malignancy of an immune privileged site. An expression and prognostic significance of HLA-F by neoplastic cells in RCC and the expression in GB is not characterized. We evaluated the expression of HLA-F specific mRNA transcripts produced by neoplastic cells in 73 cases of RCC and in 54 samples of normal kidney parenchyma. We also evaluated expression of HLA-F molecule immunohistochemically in a pilot study of 24 cases of GB (IDH-wildtype in accordance with WHO 2016 revision). The results in RCC were statistically correlated with several clinicopathological parameters. We revealed that HLA-F is up-regulated in RCC (Tab.). On the other hand, its up-regulation is counterintuitively associated with prolonged disease-free survival (Fig. 1), more favorable pT stage and lower nuclear Fuhrmann&apos;s grade. In the pilot study of GB, we found cytoplasmic expression of HLA-F (Fig. 2) in 10 cases (42%). Because of a possibility of aberrant activation of expression of non-classical HLA molecules by interferons, the identification of HLA-F status could contribute to better selection of patients with RCC who could possibly benefit from more tailored neoadjuvant biological/immunological therapy. This molecule could represent useful prognostic biomarker in RCC. Non-classical molecule HLA-F, recently proven to be a peptide presenter, physiologically protects the fetus from maternal allorecognition. Our results suggest its role in cancer immunoediting in RCC and we proved its cytopasmic expression in 42% of cases of GB. Further studies appear warrantied.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

<a href="/cs/project/NV17-32758A" target="_blank" >NV17-32758A: Imunopatologické mechanismy geneze, průběhu a léčebné odpovědi glioblastomu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů