RT info:eu-repo/semantics/article
T1 Critical role of PD-L1 expression on non-tumor cells rather than on tumor cells for efective anti-PD-L1 immunotherapy in a transplantable mouse hematopoietic tumor model
A1 Rodríguez Barbosa, José Ignacio
A1 Azuma, Miyuki
A1 Zelinskyy, Gennadiy
A1 Pérez-Simón, José-Antonio
A1 Río González, María Luisa del
A2 Sanidad Animal
K1 Veterinaria
K1 PD-1 (programmed death-1)
K1 PD-L1 (programmed death-ligand
K1 Immune checkpoint blockade
K1 Hematological malignancies
K1 CRISPR/Cas9
AB [EN] The expression of PD-L1 on tumor cells or within the tumor microenvironment has been associated with good prognosis and sustained clinical responses in immunotherapeutic regimens based on PD-L1/PD-1/CD80 immune checkpoint blockade. To look into the current controversy in cancer immunotherapy of the relative importance of PD-L1 expression on tumor cells versus non-tumor cells of the tumor microenvironment, a hematological mouse tumor model was chosen. By combining a genetic CRISPR/Cas9 and immunotherapeutic approach and using a syngeneic hematopoietic transplantable tumor model (E.G7-cOVA tumor cells), we demonstrated that dual blockade of PD-L1 interaction with PD-1 and CD80 enhanced anti-tumor immune responses that either delayed tumor growth or led to its complete eradication. PD-L1 expression on non-tumor cells of the tumor microenvironment was required for the promotion of tumor immune escape and its blockade elicited potent anti-tumor responses to PD-L1 WT and to PD-L1-defcient tumor cells. PD-L1+ tumors implanted in PDL1-defcient mice exhibited delayed tumor growth independently of PD-L1 blockade. These fndings emphasize that PD-L1 expression on non-tumor cells plays a major role in this tumor model. These observations should turn our attention to the tumor microenvironment in hematological malignancies because of its unappreciated contribution to create a conditioned niche for the tumor to grow and evade the anti-tumor immune response.
PB Springer
SN 0340-7004
LK https://hdl.handle.net/10612/17569
UL https://hdl.handle.net/10612/17569
NO Rodriguez-Barbosa, J. I., Azuma, M., Zelinskyy, G., Perez-Simon, J. A., & Del Rio, M. L. (2020). Critical role of PD-L1 expression on non-tumor cells rather than on tumor cells for effective anti-PD-L1 immunotherapy in a transplantable mouse hematopoietic tumor model. Cancer Immunology, Immunotherapy, 69(6), 1001-1014.
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 09-jun-2024