The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade–mediated tumor regression
Open accessAbstract
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.
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Cites
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Self-citationSafety and activity of anti-PD-L1 antibody in patients with advanced cancer
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Self-citationTumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
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Self-citationDiversity, Mechanisms, and Significance of Macrophage Plasticity
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Macrophages and metabolism in the tumor microenvironment
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Clinical implications of T cell exhaustion for cancer immunotherapy
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Metadata
- Authors
- Lin, H., Wei, S., Hurt, E. M., Green, M. D., Zhao, L., Vatan, L., Szeliga, W., Herbst, R., Harms, P. W., Fecher, L. A., Vats, P., Chinnaiyan, A. M., Lao, C. D., Lawrence, T. S., Wicha, M., Hamanishi, J., Mandai, M., Kryczek, I., & Zou, W.
- Venue
- Journal of Clinical Investigation
- Published
- 2018-01-16
- Volume
- 128
- Issue
- 2
- Pages
- 805-815
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2782998220
- Cited by
- 584
- References
- 12
- FWCI
- 25.45
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Lin, H., Wei, S., Hurt, E. M., Green, M. D., Zhao, L., Vatan, L., Szeliga, W., Herbst, R., Harms, P. W., Fecher, L. A., Vats, P., Chinnaiyan, A. M., Lao, C. D., Lawrence, T. S., Wicha, M., Hamanishi, J., Mandai, M., Kryczek, I., & Zou, W. (2018). Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade–mediated tumor regression. Journal of Clinical Investigation. https://doi.org/10.1172/jci96113
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