Cetuximab and IL-15 Promote NK and Dendritic Cell Activation In Vitro in Triple Negative Breast Cancer
Triple Negative Breast Cancer (TNBC) treatment is still challenging, and immunotherapy is a potential approach in this tumor subtype. Cetuximab is an IgG1 monoclonal antibody (mAb) directed against Epidermic Growth Factor Receptor (EGFR), a protein overexpressed in a subgroup of TNBC patients and as...
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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/7/1573 |
| _version_ | 1797563950895726592 |
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| author | Estefanía Paula Juliá José Mordoh Estrella Mariel Levy |
| author_facet | Estefanía Paula Juliá José Mordoh Estrella Mariel Levy |
| author_sort | Estefanía Paula Juliá |
| collection | DOAJ |
| description | Triple Negative Breast Cancer (TNBC) treatment is still challenging, and immunotherapy is a potential approach in this tumor subtype. Cetuximab is an IgG1 monoclonal antibody (mAb) directed against Epidermic Growth Factor Receptor (EGFR), a protein overexpressed in a subgroup of TNBC patients and associated with poor prognosis. Previously, we demonstrated in vitro that Cetuximab triggers Ab-dependent cell cytotoxicity against TNBC cells. In this study, using co-cultures including TNBC cells, and NK and Dendritic Cells (DCs) from healthy donors, we studied the effect of Cetuximab-activated NK cells on DC function. Given that we already demonstrated that TNBC has an immunosuppressive effect on NK cells, we also tested Cetuximab combination with IL-15. We determined that Cetuximab opsonization of TNBC cells increased IFN-γ and TNF-α production by NK cells co-cultured with DCs. Moreover, we showed that NK cells activated by TNBC cells opsonized with Cetuximab promoted tumor material uptake and maturation of DCs, as well as their ability to produce IL-12. Furthermore, the stimulation with IL-15 increased the activation of NK cells and the maturation of DCs. These results suggest that IL-15 may enhance the efficacy of Cetuximab in the treatment of TNBC by promoting activation of both NK cells and DCs. |
| first_indexed | 2024-03-10T18:50:29Z |
| format | Article |
| id | doaj.art-88fbc030864946298a5486a10729dda3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:50:29Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-88fbc030864946298a5486a10729dda32023-11-20T05:11:37ZengMDPI AGCells2073-44092020-06-0197157310.3390/cells9071573Cetuximab and IL-15 Promote NK and Dendritic Cell Activation In Vitro in Triple Negative Breast CancerEstefanía Paula Juliá0José Mordoh1Estrella Mariel Levy2Centro de Investigaciones Oncológicas CIO-FUCA, Ciudad Autónoma de Buenos Aires C1426AOE, ArgentinaCentro de Investigaciones Oncológicas CIO-FUCA, Ciudad Autónoma de Buenos Aires C1426AOE, ArgentinaCentro de Investigaciones Oncológicas CIO-FUCA, Ciudad Autónoma de Buenos Aires C1426AOE, ArgentinaTriple Negative Breast Cancer (TNBC) treatment is still challenging, and immunotherapy is a potential approach in this tumor subtype. Cetuximab is an IgG1 monoclonal antibody (mAb) directed against Epidermic Growth Factor Receptor (EGFR), a protein overexpressed in a subgroup of TNBC patients and associated with poor prognosis. Previously, we demonstrated in vitro that Cetuximab triggers Ab-dependent cell cytotoxicity against TNBC cells. In this study, using co-cultures including TNBC cells, and NK and Dendritic Cells (DCs) from healthy donors, we studied the effect of Cetuximab-activated NK cells on DC function. Given that we already demonstrated that TNBC has an immunosuppressive effect on NK cells, we also tested Cetuximab combination with IL-15. We determined that Cetuximab opsonization of TNBC cells increased IFN-γ and TNF-α production by NK cells co-cultured with DCs. Moreover, we showed that NK cells activated by TNBC cells opsonized with Cetuximab promoted tumor material uptake and maturation of DCs, as well as their ability to produce IL-12. Furthermore, the stimulation with IL-15 increased the activation of NK cells and the maturation of DCs. These results suggest that IL-15 may enhance the efficacy of Cetuximab in the treatment of TNBC by promoting activation of both NK cells and DCs.https://www.mdpi.com/2073-4409/9/7/1573NK cellsdendritic cellsADCCCetuximabtriple negative breast cancer |
| spellingShingle | Estefanía Paula Juliá José Mordoh Estrella Mariel Levy Cetuximab and IL-15 Promote NK and Dendritic Cell Activation In Vitro in Triple Negative Breast Cancer Cells NK cells dendritic cells ADCC Cetuximab triple negative breast cancer |
| title | Cetuximab and IL-15 Promote NK and Dendritic Cell Activation In Vitro in Triple Negative Breast Cancer |
| title_full | Cetuximab and IL-15 Promote NK and Dendritic Cell Activation In Vitro in Triple Negative Breast Cancer |
| title_fullStr | Cetuximab and IL-15 Promote NK and Dendritic Cell Activation In Vitro in Triple Negative Breast Cancer |
| title_full_unstemmed | Cetuximab and IL-15 Promote NK and Dendritic Cell Activation In Vitro in Triple Negative Breast Cancer |
| title_short | Cetuximab and IL-15 Promote NK and Dendritic Cell Activation In Vitro in Triple Negative Breast Cancer |
| title_sort | cetuximab and il 15 promote nk and dendritic cell activation in vitro in triple negative breast cancer |
| topic | NK cells dendritic cells ADCC Cetuximab triple negative breast cancer |
| url | https://www.mdpi.com/2073-4409/9/7/1573 |
| work_keys_str_mv | AT estefaniapaulajulia cetuximabandil15promotenkanddendriticcellactivationinvitrointriplenegativebreastcancer AT josemordoh cetuximabandil15promotenkanddendriticcellactivationinvitrointriplenegativebreastcancer AT estrellamariellevy cetuximabandil15promotenkanddendriticcellactivationinvitrointriplenegativebreastcancer |