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Can circulating PD-1, PD-L1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels enhance prognostic power of CA125 in patients with advanced high-grade serous ovarian cancer?

The most common subtype of ovarian cancer (OC) is the high-grade serous ovarian carcinoma (HGSOC), accounting for 70%–80% of all OC deaths. Although HGSOC is a potentially immunogenic tumor, clinical studies assessing the effectiveness of inhibitors of programmed death protein and its ligand (PD-1/P...

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Autores principales: Fanale, Daniele, Corsini, Lidia Rita, Brando, Chiara, Cutaia, Sofia, Di Donna, Mariano Catello, Filorizzo, Clarissa, Lisanti, Maria Chiara, Randazzo, Ugo, Magrin, Luigi, Romano, Raffaella, Bazan Russo, Tancredi Didier, Olive, Daniel, Vieni, Salvatore, Pantuso, Gianni, Chiantera, Vito, Russo, Antonio, Bazan, Viviana, Iovanna, Juan Lucio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532861/
https://www.ncbi.nlm.nih.gov/pubmed/36212445
http://dx.doi.org/10.3389/fonc.2022.946319
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author Fanale, Daniele
Corsini, Lidia Rita
Brando, Chiara
Cutaia, Sofia
Di Donna, Mariano Catello
Filorizzo, Clarissa
Lisanti, Maria Chiara
Randazzo, Ugo
Magrin, Luigi
Romano, Raffaella
Bazan Russo, Tancredi Didier
Olive, Daniel
Vieni, Salvatore
Pantuso, Gianni
Chiantera, Vito
Russo, Antonio
Bazan, Viviana
Iovanna, Juan Lucio
author_facet Fanale, Daniele
Corsini, Lidia Rita
Brando, Chiara
Cutaia, Sofia
Di Donna, Mariano Catello
Filorizzo, Clarissa
Lisanti, Maria Chiara
Randazzo, Ugo
Magrin, Luigi
Romano, Raffaella
Bazan Russo, Tancredi Didier
Olive, Daniel
Vieni, Salvatore
Pantuso, Gianni
Chiantera, Vito
Russo, Antonio
Bazan, Viviana
Iovanna, Juan Lucio
author_sort Fanale, Daniele
collection PubMed
description The most common subtype of ovarian cancer (OC) is the high-grade serous ovarian carcinoma (HGSOC), accounting for 70%–80% of all OC deaths. Although HGSOC is a potentially immunogenic tumor, clinical studies assessing the effectiveness of inhibitors of programmed death protein and its ligand (PD-1/PD-L1) in OC patients so far showed only response rates <15%. However, recent studies revealed an interesting prognostic role of plasma PD-1/PD-L1 and other circulating immunoregulatory molecules, such as the B- and T-lymphocyte attenuator (BTLA), butyrophilin sub-family 3A/CD277 receptors (BTN3A), and butyrophilin sub-family 2 member A1 (BTN2A1), in several solid tumors. Since evidence showed the prognostic relevance of pretreatment serum CA125 levels in OC, the aim of our study was to investigate if soluble forms of inhibitory immune checkpoints can enhance prognostic power of CA125 in advanced HGSOC women. Using specific ELISA tests, we examined the circulating PD-1, PD-L1, pan-BTN3As, BTN3A1, BTN2A1, and BTLA levels in 100 advanced HGSOC patients before treatment, correlating them with baseline serum CA125, age at diagnosis, body mass index (BMI), and peritoneal carcinomatosis. A multivariate analysis revealed that plasma BTN3A1 ≤4.75 ng/ml (HR, 1.94; 95% CI, 1.23–3.07; p=0.004), age at diagnosis ≤60 years (HR, 1.65; 95% CI, 1.05–2.59; p=0.03) and absence of peritoneal carcinomatosis (HR, 2.65; 95% CI, 1.66–4.22; p<0.0001) were independent prognostic factors for a longer progression-free survival (PFS) (≥30 months) in advanced HGSOC women. However, further two-factor multivariate analyses highlighted that baseline serum CA125 levels >401 U/ml and each soluble protein above respective concentration cutoff were covariates associated with shorter PFS (<30 months) and unfavorable clinical outcome, suggesting that contemporary measurement of both biomarkers than CA125 only could strengthen prognostic power of serum CA125 in predicting PFS of advanced HGSOC women. Plasma PD-L1, PD-1, BTN3A1, pan-sBTN3As, BTN2A1, or BTLA levels could be helpful biomarkers to increase prognostic value of CA125.
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spelling pubmed-95328612022-10-06 Can circulating PD-1, PD-L1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels enhance prognostic power of CA125 in patients with advanced high-grade serous ovarian cancer? Fanale, Daniele Corsini, Lidia Rita Brando, Chiara Cutaia, Sofia Di Donna, Mariano Catello Filorizzo, Clarissa Lisanti, Maria Chiara Randazzo, Ugo Magrin, Luigi Romano, Raffaella Bazan Russo, Tancredi Didier Olive, Daniel Vieni, Salvatore Pantuso, Gianni Chiantera, Vito Russo, Antonio Bazan, Viviana Iovanna, Juan Lucio Front Oncol Oncology The most common subtype of ovarian cancer (OC) is the high-grade serous ovarian carcinoma (HGSOC), accounting for 70%–80% of all OC deaths. Although HGSOC is a potentially immunogenic tumor, clinical studies assessing the effectiveness of inhibitors of programmed death protein and its ligand (PD-1/PD-L1) in OC patients so far showed only response rates <15%. However, recent studies revealed an interesting prognostic role of plasma PD-1/PD-L1 and other circulating immunoregulatory molecules, such as the B- and T-lymphocyte attenuator (BTLA), butyrophilin sub-family 3A/CD277 receptors (BTN3A), and butyrophilin sub-family 2 member A1 (BTN2A1), in several solid tumors. Since evidence showed the prognostic relevance of pretreatment serum CA125 levels in OC, the aim of our study was to investigate if soluble forms of inhibitory immune checkpoints can enhance prognostic power of CA125 in advanced HGSOC women. Using specific ELISA tests, we examined the circulating PD-1, PD-L1, pan-BTN3As, BTN3A1, BTN2A1, and BTLA levels in 100 advanced HGSOC patients before treatment, correlating them with baseline serum CA125, age at diagnosis, body mass index (BMI), and peritoneal carcinomatosis. A multivariate analysis revealed that plasma BTN3A1 ≤4.75 ng/ml (HR, 1.94; 95% CI, 1.23–3.07; p=0.004), age at diagnosis ≤60 years (HR, 1.65; 95% CI, 1.05–2.59; p=0.03) and absence of peritoneal carcinomatosis (HR, 2.65; 95% CI, 1.66–4.22; p<0.0001) were independent prognostic factors for a longer progression-free survival (PFS) (≥30 months) in advanced HGSOC women. However, further two-factor multivariate analyses highlighted that baseline serum CA125 levels >401 U/ml and each soluble protein above respective concentration cutoff were covariates associated with shorter PFS (<30 months) and unfavorable clinical outcome, suggesting that contemporary measurement of both biomarkers than CA125 only could strengthen prognostic power of serum CA125 in predicting PFS of advanced HGSOC women. Plasma PD-L1, PD-1, BTN3A1, pan-sBTN3As, BTN2A1, or BTLA levels could be helpful biomarkers to increase prognostic value of CA125. Frontiers Media S.A. 2022-09-21 /pmc/articles/PMC9532861/ /pubmed/36212445 http://dx.doi.org/10.3389/fonc.2022.946319 Text en Copyright © 2022 Fanale, Corsini, Brando, Cutaia, Di Donna, Filorizzo, Lisanti, Randazzo, Magrin, Romano, Bazan Russo, Olive, Vieni, Pantuso, Chiantera, Russo, Bazan and Iovanna https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Fanale, Daniele
Corsini, Lidia Rita
Brando, Chiara
Cutaia, Sofia
Di Donna, Mariano Catello
Filorizzo, Clarissa
Lisanti, Maria Chiara
Randazzo, Ugo
Magrin, Luigi
Romano, Raffaella
Bazan Russo, Tancredi Didier
Olive, Daniel
Vieni, Salvatore
Pantuso, Gianni
Chiantera, Vito
Russo, Antonio
Bazan, Viviana
Iovanna, Juan Lucio
Can circulating PD-1, PD-L1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels enhance prognostic power of CA125 in patients with advanced high-grade serous ovarian cancer?
title Can circulating PD-1, PD-L1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels enhance prognostic power of CA125 in patients with advanced high-grade serous ovarian cancer?
title_full Can circulating PD-1, PD-L1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels enhance prognostic power of CA125 in patients with advanced high-grade serous ovarian cancer?
title_fullStr Can circulating PD-1, PD-L1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels enhance prognostic power of CA125 in patients with advanced high-grade serous ovarian cancer?
title_full_unstemmed Can circulating PD-1, PD-L1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels enhance prognostic power of CA125 in patients with advanced high-grade serous ovarian cancer?
title_short Can circulating PD-1, PD-L1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels enhance prognostic power of CA125 in patients with advanced high-grade serous ovarian cancer?
title_sort can circulating pd-1, pd-l1, btn3a1, pan-btn3as, btn2a1 and btla levels enhance prognostic power of ca125 in patients with advanced high-grade serous ovarian cancer?
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532861/
https://www.ncbi.nlm.nih.gov/pubmed/36212445
http://dx.doi.org/10.3389/fonc.2022.946319
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