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Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Lin, Heng Wei Wei, Shuang Hurt, Elaine M. Green, Michael D. Zhao, Lili Vatan, Linda Szeliga, W. Herbst, Ronald Harms, Paul W. Fecher, Leslie Anne Allen, Eliezer M. Van Chinnaiyan, Arul M. Lao, Christopher D. Lawrence, Theodore Steven Wicha, Max S. Hamanishi, Junzo Mandai, Masaki Kryczek, Ilona Zou, Weiping |
| Copyright Year | 2018 |
| Abstract | Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blockade is a promising therapy for treating cancer. However, the mechanistic contribution of host and tumor PD-L1 and PD-1 signaling to the therapeutic efficacy of PD-L1 and PD-1 blockade remains elusive. Here, we evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1 blockade and demonstrated a loss of therapeutic efficacy of PD-L1 blockade in immunodeficient mice and in PD-L1- and PD-1-deficient mice. In contrast, neither knockout nor overexpression of PD-L1 in tumor cells had an effect on PD-L1 blockade efficacy. Human and murine studies showed high levels of functional PD-L1 expression in dendritic cells and macrophages in the tumor microenvironments and draining lymph nodes. Additionally, expression of PD-L1 on dendritic cells and macrophages in ovarian cancer and melanoma patients correlated with the efficacy of treatment with either anti-PD-1 alone or in combination with anti-CTLA-4. Thus, PD-L1-expressing dendritic cells and macrophages may mechanistically shape and therapeutically predict clinical efficacy of PD-L1/PD-1 blockade. |
| Starting Page | 805 |
| Ending Page | 815 |
| Page Count | 11 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://dm5migu4zj3pb.cloudfront.net/manuscripts/120000/120803/cache/120803.1-20180321162431-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf |
| Alternate Webpage(s) | https://dm5migu4zj3pb.cloudfront.net/manuscripts/120000/120803/cache/120803.1-20180413120520-covered-32a1e1d470ff3b8bc2b20e1a0e82a20d.pdf |
| PubMed reference number | 29337305v1 |
| Alternate Webpage(s) | https://doi.org/10.1172/JCI96113 |
| DOI | 10.1172/JCI96113 |
| Journal | The Journal of clinical investigation |
| Volume Number | 128 |
| Issue Number | 2 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Apoptosis CD274 protein, human CD274 wt Allele Immunologic Deficiency Syndromes L1 childhood acute lymphoblastic leukemia Malignant neoplasm of ovary Neoplasms Parkinson Disease Patients Programmed Cell Death Protein 1 Tumor Microenvironment lymph nodes melanoma ovarian neoplasm |
| Content Type | Text |
| Resource Type | Article |
