| First Author | Lin H | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 2 | Pages | 805-815 |
| PubMed ID | 29337305 | Mgi Jnum | J:323505 |
| Mgi Id | MGI:6117903 | Doi | 10.1172/JCI96113 |
| Citation | Lin H, et al. (2018) Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression. J Clin Invest 128(2):805-815 |
| abstractText | 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. |
