Published April 2, 2018 - More info
Programmed death-1 ligand (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.
Heng Lin, Shuang Wei, Elaine M. Hurt, Michael D. Green, Lili Zhao, Linda Vatan, Wojciech Szeliga, Ronald Herbst, Paul W. Harms, Leslie A. Fecher, Pankaj Vats, Arul M. Chinnaiyan, Christopher D. Lao, Theodore S. Lawrence, Max Wicha, Junzo Hamanishi, Masaki Mandai, Ilona Kryczek, Weiping Zou
Original citation: J Clin Invest. 2018;128(2):805–815. https://doi.org/10.1172/JCI96113
Citation for this erratum: J Clin Invest. 2018;128(4):1708. https://doi.org/10.1172/JCI120803
During the preparation of this manuscript, errors were introduced into the first sentences of the Abstract and Introduction as well as the labels for Figures 2 and 3. The corrected sentences and labels are below.
Abstract, first sentence:
Programmed death–ligand 1 (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blockade is a promising therapy for treating cancer.
Introduction, first sentence:
Therapeutic blockade of programmed death–ligand 1 (PD-L1, B7-H1) or programmed cell death protein 1 (PD-1) with mAbs leads to durable tumor control in a minority of patients across many cancer histologies (1, 2).
Figure 2, D, E, F and I:
The mouse genotype should be PD-1–/–.
Figure 2, G–I:
The dotted lines should be labeled Anti–PD-1.
Figure 3, F and G:
The labels for the x axes should be ID8 TDLN.
The errors have been corrected in the HTML and PDF versions of the manuscript.
The JCI regrets the errors.
See the related article at Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade–mediated tumor regression.