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 

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?

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.946319

DOI=10.3389/fonc.2022.946319

ISSN=2234-943X

ABSTRACT=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 one hundred pretreated advanced HGSOC patients, 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 to 3.07; p=0.004), age at diagnosis ≤60 years (HR: 1.65; 95% CI: 1.05 to 2.59; p=0.03) and absence of peritoneal carcinomatosis (HR: 2.65; 95% CI: 1.66 to 4.22; p<0.0001) were independent prognostic factors for a longer PFS (≥30 months) in advanced HGSOC women. However, further analyses showed that each circulating immune checkpoint (PD-1>2.48 ng/mL, PD-L1>0.42 ng/mL, pan-BTN3As>13.06 ng/mL, BTN3A1>4.75 ng/mL, BTN2A1>5.59 ng/mL, BTLA>2.78 ng/mL) individually correlated in a statistically significant way with serum CA125>401 U/mL levels, suggesting shorter PFS (<30 months) and poor prognosis.
Plasma PD-L1, PD-1, BTN3A1, pan-sBTN3As, BTN2A1 or BTLA levels could be helpful biomarkers to increase prognostic value of CA125.