TY - JOUR
T1 - The Controversial Role of PD-1 and Its Ligands in Gynecological Malignancies
AU - Marinelli, Oliviero
AU - Annibali, Daniela
AU - Aguzzi, Cristina
AU - Tuyaerts, Sandra
AU - Amant, Frédéric
AU - Morelli, Maria Beatrice
AU - Santoni, Giorgio
AU - Amantini, Consuelo
AU - Maggi, Federica
AU - Nabissi, Massimo
PY - 2019
Y1 - 2019
N2 - The programmed death-1 (PD-1, CD279) receptor with its ligands, programmed death ligand 1 (PD-L1, CD274, B7-H1), and programmed death ligand 2 (PD-L2, CD273, B7-DC), are the key players of one of the immune checkpoint pathways inhibiting T-cell activation. PD-L1 and PD-L2 are expressed in different cancer cells and their microenvironment, including infiltrating immune cells. However, their prognostic value is still debated and their role in the tumor microenvironment has not been fully elucidated yet. Considering the importance that cancer immunotherapy with anti-PD-1 and anti-PD-L1 antibodies gained in several tumor types, in this review article we aim to discuss the role of the PD-1/PD-L1/PD-L2 axis in gynecological cancers. PD-1 ligands have been detected in ovarian, cervical, vulvar and uterine cancers, and correlation with prognosis seems dependent from their distribution. About PD-L2, very few reports are available so far in gynecological malignancies, and its role is still not completely understood. Clinical trials using anti-PD-1 or anti-PD-L1 antibodies, but not anti-PD-L2, are currently ongoing, in all types of gynecological cancers. They have shown good safety profiles in a certain cohort of patients, but response rates remain low and many aspects remain controversial. In this review, we propose possible solutions to enhance the clinical efficacy of PD-1 axis targeting therapies. Regarding PD-L2, it might be useful to better clarify its role in order to improve the efficiency of immunotherapy in female malignancies.
AB - The programmed death-1 (PD-1, CD279) receptor with its ligands, programmed death ligand 1 (PD-L1, CD274, B7-H1), and programmed death ligand 2 (PD-L2, CD273, B7-DC), are the key players of one of the immune checkpoint pathways inhibiting T-cell activation. PD-L1 and PD-L2 are expressed in different cancer cells and their microenvironment, including infiltrating immune cells. However, their prognostic value is still debated and their role in the tumor microenvironment has not been fully elucidated yet. Considering the importance that cancer immunotherapy with anti-PD-1 and anti-PD-L1 antibodies gained in several tumor types, in this review article we aim to discuss the role of the PD-1/PD-L1/PD-L2 axis in gynecological cancers. PD-1 ligands have been detected in ovarian, cervical, vulvar and uterine cancers, and correlation with prognosis seems dependent from their distribution. About PD-L2, very few reports are available so far in gynecological malignancies, and its role is still not completely understood. Clinical trials using anti-PD-1 or anti-PD-L1 antibodies, but not anti-PD-L2, are currently ongoing, in all types of gynecological cancers. They have shown good safety profiles in a certain cohort of patients, but response rates remain low and many aspects remain controversial. In this review, we propose possible solutions to enhance the clinical efficacy of PD-1 axis targeting therapies. Regarding PD-L2, it might be useful to better clarify its role in order to improve the efficiency of immunotherapy in female malignancies.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074285501&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31681606
U2 - https://doi.org/10.3389/fonc.2019.01073
DO - https://doi.org/10.3389/fonc.2019.01073
M3 - Review article
C2 - 31681606
SN - 2234-943X
VL - 9
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1073
ER -