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Combination immunotherapy with α-CTLA-4 and α-PD-L1 antibody blockade prevents immune escape and leads to complete control of metastatic osteosarcoma

Overview of attention for article published in Journal for Immunotherapy of Cancer, May 2015
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Title
Combination immunotherapy with α-CTLA-4 and α-PD-L1 antibody blockade prevents immune escape and leads to complete control of metastatic osteosarcoma
Published in
Journal for Immunotherapy of Cancer, May 2015
DOI 10.1186/s40425-015-0067-z
Pubmed ID
Authors

Danielle M Lussier, John L Johnson, Pooja Hingorani, Joseph N Blattman

Abstract

Osteosarcoma is one of the most common bone cancers in children. Most patients with metastatic osteosarcoma die of pulmonary disease and limited curative therapeutic options exist for such patients. We have previously shown that PD-1 limits the efficacy of CTL to mediate immune control of metastatic osteosarcoma in the K7M2 mouse model of pulmonary metastatic disease and that blockade of PD-1/PD-L1 interactions can partially improve survival outcomes by enhancing the function of osteosarcoma-specific CTL. However, PD-1/PD-L1 blockade-treated mice eventually succumb to disease due to selection of PD-L1 mAb-resistant tumor cells. We investigated the mechanism of tumor cell resistance after blockade, and additional combinational therapies to combat resistance. We used an implantable model of metastatic osteosarcoma, and evaluated survival using a Log-rank test. Cellular analysis of the tumor was done post-mortem with flow cytometry staining, and evaluated using a T-test to compare treatment groups. We show here that T cells infiltrating PD-L1 antibody-resistant tumors upregulate additional inhibitory receptors, notably CTLA-4, which impair their ability to mediate tumor rejection. Based on these results we have tested combination immunotherapy with α-CTLA-4 and α-PD-L1 antibody blockade in the K7M2 mouse model of metastatic osteosarcoma and show that this results in complete control of tumors in a majority of mice as well as immunity to further tumor inoculation. Thus, combinational immunotherapy approaches to block additional inhibitory pathways in patients with metastatic osteosarcoma may provide new strategies to enhance tumor clearance and resistance to disease.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 119 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 3 3%
France 2 2%
India 1 <1%
Spain 1 <1%
Unknown 112 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 26 22%
Researcher 26 22%
Student > Bachelor 12 10%
Student > Master 9 8%
Other 8 7%
Other 21 18%
Unknown 17 14%
Readers by discipline Count As %
Medicine and Dentistry 28 24%
Immunology and Microbiology 22 18%
Agricultural and Biological Sciences 21 18%
Biochemistry, Genetics and Molecular Biology 18 15%
Engineering 4 3%
Other 6 5%
Unknown 20 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 28 June 2015.
All research outputs
#3,502,339
of 5,286,208 outputs
Outputs from Journal for Immunotherapy of Cancer
#158
of 203 outputs
Outputs of similar age
#116,389
of 174,359 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#11
of 12 outputs
Altmetric has tracked 5,286,208 research outputs across all sources so far. This one is in the 29th percentile – i.e., 29% of other outputs scored the same or lower than it.
So far Altmetric has tracked 203 research outputs from this source. They receive a mean Attention Score of 3.6. This one is in the 20th percentile – i.e., 20% 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 174,359 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 12 others from the same source and published within six weeks on either side of this one. This one is in the 8th percentile – i.e., 8% of its contemporaries scored the same or lower than it.