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Reovirus enhances cytotoxicity of natural killer cells against colorectal cancer via TLR3 pathway

Overview of attention for article published in Journal of Translational Medicine, May 2021
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Title
Reovirus enhances cytotoxicity of natural killer cells against colorectal cancer via TLR3 pathway
Published in
Journal of Translational Medicine, May 2021
DOI 10.1186/s12967-021-02853-y
Pubmed ID
Authors

Shiqi Long, Yangzhuo Gu, Yuanyuan An, Xiaojin Lin, Xiaoqing Chen, Xianyao Wang, Chunxiang Liao, Weiwei Ouyang, Nianxue Wang, Zhixu He, Xing Zhao

Abstract

Cetuximab has been approved for use for first-line treatment of patients with wild-type KRAS metastatic colorectal cancer (CRC). However, treatment with cetuximab has shown limited efficacy as a CRC monotherapy. In addition, natural killer (NK) cell function is known to be severely attenuated in cancer patients. The goal of this study was to develop a new strategy to enhance antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by NK cells, in combination with cetuximab against CRC cells. Ex vivo expanded NK cells were stimulated with reovirus, and reovirus-activated NK cells mediated ADCC assay were performed on CRC cells in combination with cetuximab. The synergistic antitumor effects of reovirus-activated NK cells and cetuximab were tested on DLD-1 tumor-bearing mice. Finally, Toll-like receptor 3 (TLR3) knockdown in NK cells, along with chemical blockade of TLR3/dsRNA complex, and inhibition of the TLR3 downstream signaling pathway, were performed to explore the mechanisms by which reovirus enhances NK cell cytotoxicity. We first confirmed that exposure of NK cells to reovirus enhanced their cytotoxicity in a dose-dependent manner.We then investigated whether reovirus-activated NK cells exposed to cetuximab-bound CRC cells exhibited greater anti-tumor efficacy than either monotherapy. Co-culture of CRC cell lines with reovirus-activated NK cells indicated that NK cytotoxicity was significantly higher in combination with cetuximab, regardless of KRAS mutation status or EGFR expression level. We also found that reovirus activation of NK cells, in conjunction with cetuximab, resulted in significantly stronger anti-tumor efficacy.Finally, TLR3 knockdown, inhibition of TLR3/dsRNA complex or TBK1/IKKε demonstrated that activation of NK cells by reovirus was dependent on TLR3 and its downstream signaling pathway. This study demonstrated that combination treatment of reovirus-activated NK cells with cetuximab synergistically enhances their anti-tumor cytotoxicity, suggesting a strong candidate strategy for clinical treatment of CRC.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters 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 7 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 7 100%

Demographic breakdown

Readers by professional status Count As %
Professor 1 14%
Professor > Associate Professor 1 14%
Student > Bachelor 1 14%
Student > Master 1 14%
Unknown 3 43%
Readers by discipline Count As %
Nursing and Health Professions 1 14%
Agricultural and Biological Sciences 1 14%
Immunology and Microbiology 1 14%
Engineering 1 14%
Unknown 3 43%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 23 July 2021.
All research outputs
#12,908,521
of 20,083,595 outputs
Outputs from Journal of Translational Medicine
#1,743
of 3,508 outputs
Outputs of similar age
#188,160
of 336,594 outputs
Outputs of similar age from Journal of Translational Medicine
#1
of 1 outputs
Altmetric has tracked 20,083,595 research outputs across all sources so far. This one is in the 33rd percentile – i.e., 33% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,508 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.8. This one is in the 43rd percentile – i.e., 43% of its peers scored the same or lower than it.
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 336,594 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
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