{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["6(4)"],"submitter":["Kleinovink JW"],"pubmed_abstract":["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<sup>+</sup> 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."],"journal":["Oncoimmunology"],"pagination":["e1294299"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5414865"],"repository":["biostudies-literature"],"pubmed_title":["PD-L1 expression on malignant cells is no prerequisite for checkpoint therapy."],"pmcid":["PMC5414865"],"pubmed_authors":["Kleinovink JW","Marijt KA","Schoonderwoerd MJA","Fransen MF","van Hall T","Ossendorp F"],"additional_accession":[]},"is_claimable":false,"name":"PD-L1 expression on malignant cells is no prerequisite for checkpoint therapy.","description":"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<sup>+</sup> 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.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017","modification":"2025-04-19T19:59:59.865Z","creation":"2019-03-27T02:42:38Z"},"accession":"S-EPMC5414865","cross_references":{"pubmed":["28507803"],"doi":["10.1080/2162402X.2017.1294299"]}}