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Erschienen in: Cancer Immunology, Immunotherapy 6/2020

22.02.2020 | Original Article

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

verfasst von: Jose-Ignacio Rodriguez-Barbosa, Miyuki Azuma, Gennadiy Zelinskyy, Jose-Antonio Perez-Simon, Maria-Luisa del Rio

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 6/2020

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Abstract

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-deficient tumor cells. PD-L1+ tumors implanted in PD-L1-deficient mice exhibited delayed tumor growth independently of PD-L1 blockade. These findings 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.
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Metadaten
Titel
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
verfasst von
Jose-Ignacio Rodriguez-Barbosa
Miyuki Azuma
Gennadiy Zelinskyy
Jose-Antonio Perez-Simon
Maria-Luisa del Rio
Publikationsdatum
22.02.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 6/2020
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-020-02520-z

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