Hodgkin lymphoma (HL) is a neoplastic disease in which the inflammatory microenvironment plays a pivotal role in the tumorigenesis. Neutrophilia is a typical finding in HL at diagnosis and, in particular, in association with lymphocytopenia, is a negative prognostic factor. As the immune checkpoint Programmed Death (PD)-L1/PD-1 has become an important therapeutic target, we were interested in the expression of PD-L1 in peripheral blood (PB) leukocytes using flow cytometry and RT-PCR in patients with HL and healthy controls. Granulocytes were the major PB cell fraction expressing PD-L1. PD-L1 expression on granulocytes was higher in patients with HL than in controls and correlated with lower T-cell numbers in PB. We analyzed for associations between PD-L1 expression in PB granulocytes at the time of diagnosis with patient characteristics and outcome in 126 patients with HL treated with standard chemotherapy adriamycin, bleomycin, vinblastine, and dacarbazine. Increased PD-L1 expression in PB associated with advanced disease, systemic symptoms, positive interim positron emission tomography, and inferior progression-free survival (PFS). PFS at 4 years was 81% (95% C.I., 71–87%) in patients with normal PD-L1 expression and 56% (95% C.I., 35–72%) in patients with higher-than-normal PD-L1 expression (p = 0.002). In conclusion, PD-L1 expression in PB could become a potentially actionable prognostic factor in HL.

Cuccaro, A., Bellesi, S., Galli, E., Zangrilli, I., Corrente, F., Cupelli, E., Fatone, F., Maiolo, E., Alma, E., Viscovo, M., D'Alo, F., Annunziata, S., Martini, M., Rufini, V., Giordano, A., De Stefano, V., Larocca, L. M., Hohaus, S., PD-L1 expression in peripheral blood granulocytes at diagnosis as prognostic factor in classical Hodgkin lymphoma, <<JOURNAL OF LEUKOCYTE BIOLOGY>>, 2022; (N/A): 1-6. [doi:10.1002/JLB.5AB0121-041R] [http://hdl.handle.net/10807/210262]

PD-L1 expression in peripheral blood granulocytes at diagnosis as prognostic factor in classical Hodgkin lymphoma

Cuccaro, Annarosa;Bellesi, Silvia;Galli, Eugenio;Corrente, Francesco;Cupelli, Elisa;Fatone, Federica;Alma, Eleonora;Viscovo, Marcello;D'Alo, F.;Annunziata, Salvatore;Martini, M.;Rufini, Vittoria;Giordano, Alessandro;De Stefano, Valerio;Larocca, Luigi Maria;Hohaus, Stefan
2022

Abstract

Hodgkin lymphoma (HL) is a neoplastic disease in which the inflammatory microenvironment plays a pivotal role in the tumorigenesis. Neutrophilia is a typical finding in HL at diagnosis and, in particular, in association with lymphocytopenia, is a negative prognostic factor. As the immune checkpoint Programmed Death (PD)-L1/PD-1 has become an important therapeutic target, we were interested in the expression of PD-L1 in peripheral blood (PB) leukocytes using flow cytometry and RT-PCR in patients with HL and healthy controls. Granulocytes were the major PB cell fraction expressing PD-L1. PD-L1 expression on granulocytes was higher in patients with HL than in controls and correlated with lower T-cell numbers in PB. We analyzed for associations between PD-L1 expression in PB granulocytes at the time of diagnosis with patient characteristics and outcome in 126 patients with HL treated with standard chemotherapy adriamycin, bleomycin, vinblastine, and dacarbazine. Increased PD-L1 expression in PB associated with advanced disease, systemic symptoms, positive interim positron emission tomography, and inferior progression-free survival (PFS). PFS at 4 years was 81% (95% C.I., 71–87%) in patients with normal PD-L1 expression and 56% (95% C.I., 35–72%) in patients with higher-than-normal PD-L1 expression (p = 0.002). In conclusion, PD-L1 expression in PB could become a potentially actionable prognostic factor in HL.
2022
Inglese
Cuccaro, A., Bellesi, S., Galli, E., Zangrilli, I., Corrente, F., Cupelli, E., Fatone, F., Maiolo, E., Alma, E., Viscovo, M., D'Alo, F., Annunziata, S., Martini, M., Rufini, V., Giordano, A., De Stefano, V., Larocca, L. M., Hohaus, S., PD-L1 expression in peripheral blood granulocytes at diagnosis as prognostic factor in classical Hodgkin lymphoma, <<JOURNAL OF LEUKOCYTE BIOLOGY>>, 2022; (N/A): 1-6. [doi:10.1002/JLB.5AB0121-041R] [http://hdl.handle.net/10807/210262]
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