Cargando…
Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma
BACKGROUND: The interaction of programmed death-1 protein (PD-1) and programmed death-1 ligand (PD-L1) produces immunosuppressive activity, protecting tumor cells from anti-tumor immunity and possibly releasing soluble PD-L1 (sPD-L1) from PD-L1 expressing tumor cells. Therefore, we measured serum le...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020571/ https://www.ncbi.nlm.nih.gov/pubmed/32054467 http://dx.doi.org/10.1186/s12885-020-6612-2 |
_version_ | 1783497775627894784 |
---|---|
author | Cho, Inju Lee, Hansang Yoon, Sang Eun Ryu, Kyung Ju Ko, Young Hyeh Kim, Won Seog Kim, Seok Jin |
author_facet | Cho, Inju Lee, Hansang Yoon, Sang Eun Ryu, Kyung Ju Ko, Young Hyeh Kim, Won Seog Kim, Seok Jin |
author_sort | Cho, Inju |
collection | PubMed |
description | BACKGROUND: The interaction of programmed death-1 protein (PD-1) and programmed death-1 ligand (PD-L1) produces immunosuppressive activity, protecting tumor cells from anti-tumor immunity and possibly releasing soluble PD-L1 (sPD-L1) from PD-L1 expressing tumor cells. Therefore, we measured serum levels of sPD-L1 in patients with primary central nervous system lymphoma (PCNSL) and explored its clinical implications. METHODS: Sixty-eight patients with newly diagnosed PCNSL had diffuse large B-cell lymphoma and were treated with high-dose methotrexate-containing chemotherapy. The measurement of sPD-L1 and cytokines was performed using serum samples archived at diagnosis, and the tissue expression of PD-L1 was also analyzed from archived paraffin-embedded tissue blocks. Disease relapse, progression-free survival (PFS), and overall survival (OS) were analyzed according to the extent of sPD-L1 in serum and PD-L1 in tissue. RESULTS: The median level of serum sPD-L1 (0.429 ng/mL) was higher than in healthy control patients (0.364 ng/mL). The occurrence of relapse was more frequent in the high sPD-L1 (78%) than the low sPD-L1 group (50%), though the groups did not have different clinical or pathological characteristics at diagnosis. As a result, the OS and PFS for the high sPD-L1 group were significantly lower than those in the low group. PD-L1-positive tumor cells were found in 35 patients (67%), and the extent of PD-L1-postive tumor cells was positively associated with serum sPD-L1 levels (r = 0.299, P = 0.031). Among the 34 cytokines analyzed, only the serum level of IL-7 correlated with the serum level of sPD-L1 (r = 0.521, P < 0.001). CONCLUSIONS: Serum levels of sPD-L1 could reflect the expression of PD-L1 in PCNSL tumor cells and predict patient survival outcomes. Therefore, sPD-L1 in serum could be a feasible biomarker for determining a risk-adapted treatment strategy for PCNSL patients. TRIAL REGISTRATION: The study population was patients who were diagnosed with PCNSL between January 2009 and February 2017 and registered for our prospective cohort studies after providing written informed consent (ClinicalTrials.gov: NCT00822731 [date of registration - January 14, 2009] and NCT01877109 [date of registration - June 13, 2013]). |
format | Online Article Text |
id | pubmed-7020571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-70205712020-02-20 Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma Cho, Inju Lee, Hansang Yoon, Sang Eun Ryu, Kyung Ju Ko, Young Hyeh Kim, Won Seog Kim, Seok Jin BMC Cancer Research Article BACKGROUND: The interaction of programmed death-1 protein (PD-1) and programmed death-1 ligand (PD-L1) produces immunosuppressive activity, protecting tumor cells from anti-tumor immunity and possibly releasing soluble PD-L1 (sPD-L1) from PD-L1 expressing tumor cells. Therefore, we measured serum levels of sPD-L1 in patients with primary central nervous system lymphoma (PCNSL) and explored its clinical implications. METHODS: Sixty-eight patients with newly diagnosed PCNSL had diffuse large B-cell lymphoma and were treated with high-dose methotrexate-containing chemotherapy. The measurement of sPD-L1 and cytokines was performed using serum samples archived at diagnosis, and the tissue expression of PD-L1 was also analyzed from archived paraffin-embedded tissue blocks. Disease relapse, progression-free survival (PFS), and overall survival (OS) were analyzed according to the extent of sPD-L1 in serum and PD-L1 in tissue. RESULTS: The median level of serum sPD-L1 (0.429 ng/mL) was higher than in healthy control patients (0.364 ng/mL). The occurrence of relapse was more frequent in the high sPD-L1 (78%) than the low sPD-L1 group (50%), though the groups did not have different clinical or pathological characteristics at diagnosis. As a result, the OS and PFS for the high sPD-L1 group were significantly lower than those in the low group. PD-L1-positive tumor cells were found in 35 patients (67%), and the extent of PD-L1-postive tumor cells was positively associated with serum sPD-L1 levels (r = 0.299, P = 0.031). Among the 34 cytokines analyzed, only the serum level of IL-7 correlated with the serum level of sPD-L1 (r = 0.521, P < 0.001). CONCLUSIONS: Serum levels of sPD-L1 could reflect the expression of PD-L1 in PCNSL tumor cells and predict patient survival outcomes. Therefore, sPD-L1 in serum could be a feasible biomarker for determining a risk-adapted treatment strategy for PCNSL patients. TRIAL REGISTRATION: The study population was patients who were diagnosed with PCNSL between January 2009 and February 2017 and registered for our prospective cohort studies after providing written informed consent (ClinicalTrials.gov: NCT00822731 [date of registration - January 14, 2009] and NCT01877109 [date of registration - June 13, 2013]). BioMed Central 2020-02-13 /pmc/articles/PMC7020571/ /pubmed/32054467 http://dx.doi.org/10.1186/s12885-020-6612-2 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Cho, Inju Lee, Hansang Yoon, Sang Eun Ryu, Kyung Ju Ko, Young Hyeh Kim, Won Seog Kim, Seok Jin Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma |
title | Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma |
title_full | Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma |
title_fullStr | Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma |
title_full_unstemmed | Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma |
title_short | Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma |
title_sort | serum levels of soluble programmed death-ligand 1 (spd-l1) in patients with primary central nervous system diffuse large b-cell lymphoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020571/ https://www.ncbi.nlm.nih.gov/pubmed/32054467 http://dx.doi.org/10.1186/s12885-020-6612-2 |
work_keys_str_mv | AT choinju serumlevelsofsolubleprogrammeddeathligand1spdl1inpatientswithprimarycentralnervoussystemdiffuselargebcelllymphoma AT leehansang serumlevelsofsolubleprogrammeddeathligand1spdl1inpatientswithprimarycentralnervoussystemdiffuselargebcelllymphoma AT yoonsangeun serumlevelsofsolubleprogrammeddeathligand1spdl1inpatientswithprimarycentralnervoussystemdiffuselargebcelllymphoma AT ryukyungju serumlevelsofsolubleprogrammeddeathligand1spdl1inpatientswithprimarycentralnervoussystemdiffuselargebcelllymphoma AT koyounghyeh serumlevelsofsolubleprogrammeddeathligand1spdl1inpatientswithprimarycentralnervoussystemdiffuselargebcelllymphoma AT kimwonseog serumlevelsofsolubleprogrammeddeathligand1spdl1inpatientswithprimarycentralnervoussystemdiffuselargebcelllymphoma AT kimseokjin serumlevelsofsolubleprogrammeddeathligand1spdl1inpatientswithprimarycentralnervoussystemdiffuselargebcelllymphoma |