| Title |
Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors
|
|---|---|
| Published in |
Cancer Immunology Research, September 2015
|
| DOI | 10.1158/2326-6066.cir-14-0214 |
| Pubmed ID | |
| Authors |
Edwin R Manuel, Jeremy Chen, Massimo D'Apuzzo, Melanie G Lampa, Teodora I Kaltcheva, Curtis B Thompson, Thomas Ludwig, Vincent Chung, Don J Diamond |
| Abstract |
Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms, such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for more than 25 years. Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed extended survival with frequent total regression of autochthonous and orthotopic PDAC tumors. This observation was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not seen using a scrambled control (shScr-ST). Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex vivo through mechanisms involving FasL and serine proteases. In addition, CD8(+) T cells were observed to contribute to late control of pancreatic tumors. Collectively, our data demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated by PEGPH20-mediated HA removal, further highlighting an important component of effective treatment for PDAC. Cancer Immunol Res; 1-12. ©2015 AACR. |
X Demographics
The data shown below were collected from the profiles of 11 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 4 | 36% |
| United States | 2 | 18% |
| Cameroon | 1 | 9% |
| China | 1 | 9% |
| Unknown | 3 | 27% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 7 | 64% |
| Scientists | 3 | 27% |
| Practitioners (doctors, other healthcare professionals) | 1 | 9% |
Mendeley readers
The data shown below were compiled from readership statistics for 68 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 1% |
| Unknown | 67 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 13 | 19% |
| Student > Ph. D. Student | 10 | 15% |
| Student > Doctoral Student | 7 | 10% |
| Student > Bachelor | 6 | 9% |
| Other | 5 | 7% |
| Other | 9 | 13% |
| Unknown | 18 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 15 | 22% |
| Agricultural and Biological Sciences | 10 | 15% |
| Medicine and Dentistry | 8 | 12% |
| Immunology and Microbiology | 5 | 7% |
| Chemistry | 3 | 4% |
| Other | 4 | 6% |
| Unknown | 23 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 15. 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 10 October 2023.
All research outputs
#2,491,267
of 25,775,807 outputs
Outputs from Cancer Immunology Research
#270
of 1,593 outputs
Outputs of similar age
#31,485
of 277,867 outputs
Outputs of similar age from Cancer Immunology Research
#6
of 47 outputs
Altmetric has tracked 25,775,807 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,593 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.1. This one has done well, scoring higher than 82% 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 277,867 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 88% of its contemporaries.
We're also able to compare this research output to 47 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 87% of its contemporaries.