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Interleukin-15 is required for immunosurveillance and immunoprevention of HER2/neu-driven mammary carcinogenesis

Overview of attention for article published in Breast Cancer Research, May 2015
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Title
Interleukin-15 is required for immunosurveillance and immunoprevention of HER2/neu-driven mammary carcinogenesis
Published in
Breast Cancer Research, May 2015
DOI 10.1186/s13058-015-0588-x
Pubmed ID
Authors

Stefania Croci, Patrizia Nanni, Arianna Palladini, Giordano Nicoletti, Valentina Grosso, Giorgia Benegiamo, Lorena Landuzzi, Alessia Lamolinara, Marianna L. Ianzano, Dario Ranieri, Massimiliano Dall’Ora, Manuela Iezzi, Carla De Giovanni, Pier-Luigi Lollini

Abstract

We previously demonstrated that HER2/neu-driven mammary carcinogenesis can be prevented by an interleukin-12 (IL-12)-adjuvanted allogeneic HER2/neu-expressing cell vaccine. Since IL-12 can induce the release of interleukin-15 (IL-15), in the present study we investigated the role played by IL-15 in HER2/neu driven mammary carcinogenesis and in its immune prevention. HER2/neu transgenic mice with homozygous knockout of IL-15 (here referred to as IL15KO/NeuT mice) were compared to IL-15 wild-type HER2/neu transgenic mice (NeuT) regarding mammary carcinogenesis, profile of peripheral blood lymphocytes and splenocytes and humoral and cellular responses induced by the vaccine. IL15KO/NeuT mice showed a significantly earlier mammary cancer onset than NeuT mice, with median latency times of 16 and 20 weeks respectively, suggesting a role for IL-15 in cancer immunosurveillance. Natural killer (NK) and CD8+ lymphocytes were significantly lower in IL15KO/NeuT mice compared to mice with wild-type IL-15. The IL-12-adjuvanted allogeneic HER2/neu-expressing cell vaccine was still able to delay mammary cancer onset but efficacy in IL-15-lacking mice vanished earlier: all vaccinated IL15KO/NeuT mice developed tumors within 80 weeks of age (median latency of 53 weeks), whereas more than 70 % vaccinated NeuT mice remained tumor-free up to 80 weeks of age. Vaccinated IL15KO/NeuT mice showed less necrotic tumors with fewer CD3+ and lacked perforin-positive infiltrating cells compared to NeuT mice. Concerning the anti-vaccine antibody response, antibody titer was unaffected by the lack of IL-15, but less antibodies of IgM and IgG1 isotypes were found in IL15KO/NeuT mice. A lower induction by vaccine of systemic interferon-gamma (IFN-γ) and interleukin-5 (IL-5) was also observed in IL15KO/NeuT mice when compared to NeuT mice. Finally, we found a lower level of CD8+ memory cells in peripheral blood of vaccinated IL15KO/NeuT respect to NeuT mice. We demonstrated that IL-15 has a role in mammary cancer immunosurveillance and that IL-15-regulated NK and CD8+ memory cells play a role in long-lasting immunoprevention, further supporting the potential use of IL-15 as adjuvant in immunological strategies against tumors.

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X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
France 1 2%
Canada 1 2%
Unknown 39 95%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 8 20%
Researcher 7 17%
Student > Ph. D. Student 5 12%
Student > Doctoral Student 3 7%
Student > Postgraduate 3 7%
Other 8 20%
Unknown 7 17%
Readers by discipline Count As %
Medicine and Dentistry 10 24%
Biochemistry, Genetics and Molecular Biology 5 12%
Immunology and Microbiology 4 10%
Agricultural and Biological Sciences 4 10%
Philosophy 1 2%
Other 7 17%
Unknown 10 24%
Attention Score in Context

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 16 January 2016.
All research outputs
#17,286,645
of 25,374,917 outputs
Outputs from Breast Cancer Research
#1,535
of 2,053 outputs
Outputs of similar age
#168,854
of 281,628 outputs
Outputs of similar age from Breast Cancer Research
#28
of 38 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,053 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one is in the 19th percentile – i.e., 19% 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 281,628 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 38 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.