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Pregled bibliografske jedinice broj: 682381

The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia


Bursa, Davide; Serra, S.; Coscia, M.; Rossi, Davide, D'Arena, G.; Laurenti, L.; Jakšić, Ozren; Fedele, G.; Inghirami, G.; Gaidano, G.; Malavasi, Fabio; Deaglio, Silvia
The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia // Haematologica, 98 (2013), 6; 953-963 doi:10.3324/haematol.2012.077537 (međunarodna recenzija, članak, znanstveni)


CROSBI ID: 682381 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia

Autori
Bursa, Davide ; Serra, S. ; Coscia, M. ; Rossi, Davide, D'Arena, G. ; Laurenti, L. ; Jakšić, Ozren ; Fedele, G. ; Inghirami, G. ; Gaidano, G. ; Malavasi, Fabio ; Deaglio, Silvia

Izvornik
Haematologica (0390-6078) 98 (2013), 6; 953-963

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
CLL

Sažetak
Chronic lymphocytic leukemia is marked by profound defects in T-cell function. Programmed death-1 is a receptor involved in tumor-mediated immunosuppression through binding of the PD-L1 ligand. Multiparametric flow cytometry and immunohistochemistry were used to study PD-1/PD-L1 expression. Functional assays were used to determine the involvement of the PD-1/PD-L1 axis in T-cell responses. PD-1 expression by CD4(+) and CD8(+) T lymphocytes was significantly higher in 117 chronic lymphocytic leukemia patients than in 33 donors of a comparable age. CD4(+) and CD8(+) T lymphocytes from chronic lymphocytic leukemia patients displayed increased numbers of effector memory and terminally differentiated cells, respectively, when compared to controls. The number of effector memory CD4(+) and terminally differentiated CD8(+) lymphocytes positively associated with a more advanced stage of disease, treatment requirements and unfavorable genomic aberrations. Furthermore, leukemic lymphocytes expressed higher levels of PD-L1 than circulating B lymphocytes from normal donors. PD-1 and PD-L1 surface expression spiked in proliferating T and B lymphocytes, suggesting that this interaction works efficiently in activated environments. Within chronic lymphocytic leukemia proliferation centers in the lymph node, CD4(+)/PD-1(+) T lymphocytes were found to be in close contact with PD-L1(+) chronic lymphocytic leukemia cells. Lastly, functional experiments using recombinant soluble PD-L1 and blocking antibodies indicated that this axis contributes to the inhibition of IFN-γ production by CD8(+) T cells. These observations suggest that pharmacological manipulation of the PD-1/PD-L1 axis may contribute to restoring T-cell functions in the chronic lymphocytic leukemia microenvironment.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti



POVEZANOST RADA


Projekti:
198-1980955-0953 - Imunobiologija kronične B-limfocitne leukemije i mikrookoliš (Jakšić, Ozren, MZOS ) ( POIROT)

Ustanove:
Klinička bolnica "Dubrava"

Profili:

Avatar Url Ozren Jakšić (autor)

Citiraj ovu publikaciju

Bursa, Davide; Serra, S.; Coscia, M.; Rossi, Davide, D'Arena, G.; Laurenti, L.; Jakšić, Ozren; Fedele, G.; Inghirami, G.; Gaidano, G.; Malavasi, Fabio; Deaglio, Silvia
The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia // Haematologica, 98 (2013), 6; 953-963 doi:10.3324/haematol.2012.077537 (međunarodna recenzija, članak, znanstveni)
Bursa, D., Serra, S., Coscia, M., Rossi, Davide, D'Arena, G., Laurenti, L., Jakšić, O., Fedele, G., Inghirami, G., Gaidano, G., Malavasi, F. & Deaglio, S. (2013) The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia. Haematologica, 98 (6), 953-963 doi:10.3324/haematol.2012.077537.
@article{article, year = {2013}, pages = {953-963}, DOI = {10.3324/haematol.2012.077537}, keywords = {CLL}, journal = {Haematologica}, doi = {10.3324/haematol.2012.077537}, volume = {98}, number = {6}, issn = {0390-6078}, title = {The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia}, keyword = {CLL} }
@article{article, year = {2013}, pages = {953-963}, DOI = {10.3324/haematol.2012.077537}, keywords = {CLL}, journal = {Haematologica}, doi = {10.3324/haematol.2012.077537}, volume = {98}, number = {6}, issn = {0390-6078}, title = {The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia}, keyword = {CLL} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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