Sunitinib Combined with Th1 Cytokines Potentiates Apoptosis in Human Breast Cancer Cells and Suppresses Tumor Growth in a Murine Model of HER-2pos Breast Cancer
Although immune-based therapies have made remarkable inroads in cancer treatment, they usually must be combined with standard treatment modalities, including cytotoxic drugs, to achieve maximal clinical benefits. As immunotherapies are further advanced and refined, considerable efforts will be requi...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | International Journal of Breast Cancer |
| Online Access: | http://dx.doi.org/10.1155/2021/8818393 |
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| author | Nirmala Ghimirey Chase Steele Brian J. Czerniecki Gary K. Koski Loral E. Showalter |
| author_facet | Nirmala Ghimirey Chase Steele Brian J. Czerniecki Gary K. Koski Loral E. Showalter |
| author_sort | Nirmala Ghimirey |
| collection | DOAJ |
| description | Although immune-based therapies have made remarkable inroads in cancer treatment, they usually must be combined with standard treatment modalities, including cytotoxic drugs, to achieve maximal clinical benefits. As immunotherapies are further advanced and refined, considerable efforts will be required to identify combination therapies that will maximize clinical responses while simultaneously decreasing the unpleasant and sometimes life-threatening side effects of standard therapy. Over the last two decades, evidence has emerged that Th1 cytokines can play a central role in protective antitumor immunity and that combinations of Th1 cytokines can induce senescence and apoptosis in cancer cells. To explore the possibility of combining targeted drugs with Th1-polarizing vaccines, we undertook a study to examine the impact of combining Th1 cytokines with the relatively broad-spectrum receptor tyrosine kinase antagonist, sunitinib. We found that when a panel of five phenotypically diverse human breast cancer cell lines was subjected to treatment with sunitinib plus recombinant Th1 cytokines IFN-γ and TNF-α, synergistic effects were observed across a number of parameters including different aspects of apoptotic cell death. Interestingly, sunitinib was found to have a profoundly suppressive effect of T cell’s capacity to secrete IFN-γ, indicating that in vivo use of this drug may hinder robust Th1 responses. Nonetheless, this suppression was circumvented in a mouse model of HER-2pos breast disease by supplying recombinant interferon-gamma to achieve a combination therapy significantly more potent than either agent. |
| format | Article |
| id | doaj-art-6145e9530ae843b68823f7108bf8b2e1 |
| institution | Kabale University |
| issn | 2090-3170 2090-3189 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Breast Cancer |
| spelling | doaj-art-6145e9530ae843b68823f7108bf8b2e12025-02-03T05:57:51ZengWileyInternational Journal of Breast Cancer2090-31702090-31892021-01-01202110.1155/2021/88183938818393Sunitinib Combined with Th1 Cytokines Potentiates Apoptosis in Human Breast Cancer Cells and Suppresses Tumor Growth in a Murine Model of HER-2pos Breast CancerNirmala Ghimirey0Chase Steele1Brian J. Czerniecki2Gary K. Koski3Loral E. Showalter4Department of Biological Sciences, Kent State University, Kent, Ohio 44242, USADepartment of Biological Sciences, Kent State University, Kent, Ohio 44242, USADepartment of Breast Oncology, H. Lee Moffitt Cancer Center, Tampa Florida 33612, USADepartment of Biological Sciences, Kent State University, Kent, Ohio 44242, USADepartment of Biological Sciences, Kent State University, Kent, Ohio 44242, USAAlthough immune-based therapies have made remarkable inroads in cancer treatment, they usually must be combined with standard treatment modalities, including cytotoxic drugs, to achieve maximal clinical benefits. As immunotherapies are further advanced and refined, considerable efforts will be required to identify combination therapies that will maximize clinical responses while simultaneously decreasing the unpleasant and sometimes life-threatening side effects of standard therapy. Over the last two decades, evidence has emerged that Th1 cytokines can play a central role in protective antitumor immunity and that combinations of Th1 cytokines can induce senescence and apoptosis in cancer cells. To explore the possibility of combining targeted drugs with Th1-polarizing vaccines, we undertook a study to examine the impact of combining Th1 cytokines with the relatively broad-spectrum receptor tyrosine kinase antagonist, sunitinib. We found that when a panel of five phenotypically diverse human breast cancer cell lines was subjected to treatment with sunitinib plus recombinant Th1 cytokines IFN-γ and TNF-α, synergistic effects were observed across a number of parameters including different aspects of apoptotic cell death. Interestingly, sunitinib was found to have a profoundly suppressive effect of T cell’s capacity to secrete IFN-γ, indicating that in vivo use of this drug may hinder robust Th1 responses. Nonetheless, this suppression was circumvented in a mouse model of HER-2pos breast disease by supplying recombinant interferon-gamma to achieve a combination therapy significantly more potent than either agent.http://dx.doi.org/10.1155/2021/8818393 |
| spellingShingle | Nirmala Ghimirey Chase Steele Brian J. Czerniecki Gary K. Koski Loral E. Showalter Sunitinib Combined with Th1 Cytokines Potentiates Apoptosis in Human Breast Cancer Cells and Suppresses Tumor Growth in a Murine Model of HER-2pos Breast Cancer International Journal of Breast Cancer |
| title | Sunitinib Combined with Th1 Cytokines Potentiates Apoptosis in Human Breast Cancer Cells and Suppresses Tumor Growth in a Murine Model of HER-2pos Breast Cancer |
| title_full | Sunitinib Combined with Th1 Cytokines Potentiates Apoptosis in Human Breast Cancer Cells and Suppresses Tumor Growth in a Murine Model of HER-2pos Breast Cancer |
| title_fullStr | Sunitinib Combined with Th1 Cytokines Potentiates Apoptosis in Human Breast Cancer Cells and Suppresses Tumor Growth in a Murine Model of HER-2pos Breast Cancer |
| title_full_unstemmed | Sunitinib Combined with Th1 Cytokines Potentiates Apoptosis in Human Breast Cancer Cells and Suppresses Tumor Growth in a Murine Model of HER-2pos Breast Cancer |
| title_short | Sunitinib Combined with Th1 Cytokines Potentiates Apoptosis in Human Breast Cancer Cells and Suppresses Tumor Growth in a Murine Model of HER-2pos Breast Cancer |
| title_sort | sunitinib combined with th1 cytokines potentiates apoptosis in human breast cancer cells and suppresses tumor growth in a murine model of her 2pos breast cancer |
| url | http://dx.doi.org/10.1155/2021/8818393 |
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