PD-L1 expression on malignant cells is no prerequisite for checkpoint therapy

Jan Willem Kleinovink, Koen A. Marijt, Mark J. A. Schoonderwoerd, Thorbald van Hall, Ferry Ossendorp, Marieke F. Fransen

Research output: Contribution to journalArticleAcademicpeer-review


Immunotherapy with PD-1/PD-L1-blocking antibodies is clinically effective for several tumor types, but the mechanism is not fully understood. PD-L1 expression on tumor biopsies is generally regarded as an inclusion criterion for this cancer therapy. Here, we describe the PD-L1-blocking therapeutic responses of preclinical tumors in which PD-L1 expression was removed from cancer cells, but not from immune infiltrate. Lack of PD-L1 expression on malignant cells delayed tumor outgrowth in a CD8+ T cell-mediated fashion, showing the importance of this molecule in immune suppression. PD-L1 expression was evident on myeloid-infiltrating cells in the microenvironment of these tumors and targeting stromal PD-L1 with blocking antibody therapy had additional antitumor effect, demonstrating that PD-L1 on both malignant cells and immune cells is involved in the mechanism of immunotherapeutic antibodies. Importantly, comparable results were obtained with PD-1-blocking therapy. These findings have implications for inclusion of cancer patients in PD-1/PD-L1 blockade immunotherapies.
Original languageEnglish
Article numbere1294299
Issue number4
Publication statusPublished - 2017
Externally publishedYes

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