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- Title
Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated tumor regression.
- Authors
Lin, Heng; Wei, Shuang; Hurt, Elaine M; Green, Michael D; Zhao, Lili; Vatan, Linda; Szeliga, Wojciech; Herbst, Ronald; Harms, Paul W; Fecher, Leslie A; Vats, Pankaj; Chinnaiyan, Arul M; Lao, Christopher D; Lawrence, Theodore S; Wicha, Max; Hamanishi, Junzo; Mandai, Masaki; Kryczek, Ilona; Zou, Weiping
- 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.
- Publication
Journal of Clinical Investigation, 2018, Vol 128, Issue 2, p805
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI96113