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Anti-PD-1 antibody significantly increases therapeutic efficacy of Listeria monocytogenes (Lm)-LLO immunotherapy

Overview of attention for article published in Journal for Immunotherapy of Cancer, January 2013
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (84th percentile)

Mentioned by

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1 tweeter
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6 patents

Citations

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44 Dimensions

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85 Mendeley
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Title
Anti-PD-1 antibody significantly increases therapeutic efficacy of Listeria monocytogenes (Lm)-LLO immunotherapy
Published in
Journal for Immunotherapy of Cancer, January 2013
DOI 10.1186/2051-1426-1-15
Pubmed ID
Authors

Mikayel Mkrtichyan, Namju Chong, Rasha Abu Eid, Anu Wallecha, Reshma Singh, John Rothman, Samir N Khleif

Abstract

One of the significant tumor immune escape mechanisms and substantial barrier for successful immunotherapy is tumor-mediated inhibition of immune response through cell-to-cell or receptor/ligand interactions. Programmed death receptor-1 (PD-1) interaction with its ligands, PD-L1 and PD-L2, is one of the important strategies that many tumors employ to escape immune surveillance. Upon PD-Ls binding to PD-1, T cell receptor (TCR) signaling is dampened, causing inhibition of proliferation, decreased cytokine production, anergy and/or apoptosis. Thus PD-Ls expression by tumor cells serves as a protective mechanism, leading to suppression of tumor-infiltrating lymphocytes in the tumor microenvironment. Lm-LLO immunotherapies have been shown to be therapeutically effective due to their ability to induce potent antigen-specific immune responses. However, it has been demonstrated that infection with Lm leads to up-regulation of PD-L1 on mouse immune cells that can inhibit effector T cells through PD-1/PD-L1 pathway. Therapeutic and immune efficacy of Listeria-based vaccine (Lm-LLO-E7) in combination with anti-PD-1 antibody was tested in E7 antigen expressing TC-1 mouse tumor model. Tumor growth, survival, as well as peripheral and tumor-infiltrating immune cell profiles after immunotherapy were assessed. Here we demonstrate that the combination of an Lm-LLO immunotherapy with anti-PD-1 antibody that blocks PD-1/PD-L1 interaction, significantly improves immune and therapeutic efficacy of treatment in TC-1 mouse tumor model. Importantly, we show that in addition to significant reduction of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) in both spleen and tumor microenvironment that are mediated solely by the Lm-LLO immunotherapy, the addition of anti-PD-1 antibody to the treatment results in significant increase of antigen-specific immune responses in periphery and CD8 T cell infiltration into the tumor. As a result, this combinational treatment leads to significant inhibition of tumor growth and prolonged survival/complete regression of tumors in treated animals. We also demonstrate that in vitro infection with Lm results in significant upregulation of surface PD-L1 expression on human monocyte-derived dendritic cells suggesting the translational capacity of this finding. Our findings demonstrate that combination of Lm-LLO-based vaccine with blocking of PD-1/PD-L1 interaction is a feasible approach with clinical translation potential that can lead to overall enhancement of the efficacy of anti-tumor immunotherapy.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 85 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 1%
United States 1 1%
Germany 1 1%
Belgium 1 1%
Unknown 81 95%

Demographic breakdown

Readers by professional status Count As %
Researcher 29 34%
Student > Ph. D. Student 13 15%
Other 8 9%
Student > Bachelor 7 8%
Student > Doctoral Student 4 5%
Other 13 15%
Unknown 11 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 21 25%
Immunology and Microbiology 19 22%
Medicine and Dentistry 14 16%
Biochemistry, Genetics and Molecular Biology 9 11%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Other 5 6%
Unknown 14 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 July 2018.
All research outputs
#2,698,323
of 20,192,041 outputs
Outputs from Journal for Immunotherapy of Cancer
#619
of 2,365 outputs
Outputs of similar age
#37,996
of 243,990 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#1
of 1 outputs
Altmetric has tracked 20,192,041 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,365 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.9. This one has gotten more attention than average, scoring higher than 73% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 243,990 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them