{"title":"树突状细胞免疫:乳腺癌小鼠树突状细胞亚群的筛选","authors":"Alia M Aldahlawi, Kawther Sayed Ali Zaher","doi":"10.4103/jmau.jmau_85_22","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is the most devastating disease, particularly the lethal invasive form. It is the most underlying cause of death among women worldwide. The expansion of BC is controlled by a variety of alterations in the tumor cells themselves, in addition to the state of the immune system, which has a direct influence on the tumor microenvironment. Numerous receptors expressed by T-cells interact with ligands on antigen-presenting cells to provide activation signals results in mounting effector anti-tumor T-cell responses. On the other hand, there is a dearth of information about the actual interactions and reactions of T-cells and dendritic cells (DCs) all through the progression of tumor development.</p><p><strong>Aim: </strong>Immune system response against BC was investigated through tumor induction in mice. The size and volume of the tumor were calculated. Moreover, the phenotypical profile of T-cells and DCs from lymph nodes (LN) and spleens of BC-bearing mice was investigated. In addition, the levels of Transforming growth factor-β, Interferon-gamma (IFN-γ), Interleukin IL-2, IL-10, IL-4, IL-12, and tumor necrosis factor (TNF)-α were determined.</p><p><strong>Materials and methods: </strong>MDA231 cells were utilized to induce BC in 30 white BALB/C mice, whereas the other 30 mice acted as healthy controls and were not treated with any cancer-causing agents. The impact of malignancy was evaluated using flow cytometry based on the marking surface molecules, as well as the titer of specific cytokines of the mice's LN culture using the ELISA method. These cytokines included transforming growth factor-β (TGF-β), IFN-γ, IL-2, IL -10, IL -4, IL -12, and TNF-α.</p><p><strong>Results: </strong>The findings showed that the maturation of DCs was inhibited, followed by an accumulation of immature DCs. These immature DCs increase the release of TGF-β and cytokines like IL-10 and inhibit the release of IFN-γ and IL-12 in the culture supernatant of nodal lymph and spleen suspension of BC-bearing mice compared to control. In addition, there was a low expression of CD80 and CD86 on DCs, which indicates a low maturation process.</p><p><strong>Conclusion: </strong>According to the findings, the tumor microenvironment may have been responsible for preventing the maturation of DCs. This, in turn, weakened the immune response and facilitated the ability of the tumor to proliferate. Furthermore, the tumor microenvironment increased the number of immature DCs by inhibiting their stimulation by overexpression of TGF-β-produced by regulatory T lymphocytes and stimulation of tumor cells. In addition, the tumor microenvironment stimulated the secretion of cytokines such as IL-10, and CD4 and decreased the secretion of IFN-γ-and IL-12 in tumor-induced mice cultured LN and spleen.</p>","PeriodicalId":16340,"journal":{"name":"Journal of Microscopy and Ultrastructure","volume":"11 1","pages":"150-160"},"PeriodicalIF":0.0000,"publicationDate":"2023-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679829/pdf/","citationCount":"0","resultStr":"{\"title\":\"Dendritic Cell-Based Immunity: Screening of Dendritic Cell Subsets in Breast Cancer-Bearing Mice.\",\"authors\":\"Alia M Aldahlawi, Kawther Sayed Ali Zaher\",\"doi\":\"10.4103/jmau.jmau_85_22\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Breast cancer (BC) is the most devastating disease, particularly the lethal invasive form. It is the most underlying cause of death among women worldwide. The expansion of BC is controlled by a variety of alterations in the tumor cells themselves, in addition to the state of the immune system, which has a direct influence on the tumor microenvironment. Numerous receptors expressed by T-cells interact with ligands on antigen-presenting cells to provide activation signals results in mounting effector anti-tumor T-cell responses. On the other hand, there is a dearth of information about the actual interactions and reactions of T-cells and dendritic cells (DCs) all through the progression of tumor development.</p><p><strong>Aim: </strong>Immune system response against BC was investigated through tumor induction in mice. The size and volume of the tumor were calculated. Moreover, the phenotypical profile of T-cells and DCs from lymph nodes (LN) and spleens of BC-bearing mice was investigated. In addition, the levels of Transforming growth factor-β, Interferon-gamma (IFN-γ), Interleukin IL-2, IL-10, IL-4, IL-12, and tumor necrosis factor (TNF)-α were determined.</p><p><strong>Materials and methods: </strong>MDA231 cells were utilized to induce BC in 30 white BALB/C mice, whereas the other 30 mice acted as healthy controls and were not treated with any cancer-causing agents. The impact of malignancy was evaluated using flow cytometry based on the marking surface molecules, as well as the titer of specific cytokines of the mice's LN culture using the ELISA method. These cytokines included transforming growth factor-β (TGF-β), IFN-γ, IL-2, IL -10, IL -4, IL -12, and TNF-α.</p><p><strong>Results: </strong>The findings showed that the maturation of DCs was inhibited, followed by an accumulation of immature DCs. These immature DCs increase the release of TGF-β and cytokines like IL-10 and inhibit the release of IFN-γ and IL-12 in the culture supernatant of nodal lymph and spleen suspension of BC-bearing mice compared to control. In addition, there was a low expression of CD80 and CD86 on DCs, which indicates a low maturation process.</p><p><strong>Conclusion: </strong>According to the findings, the tumor microenvironment may have been responsible for preventing the maturation of DCs. This, in turn, weakened the immune response and facilitated the ability of the tumor to proliferate. Furthermore, the tumor microenvironment increased the number of immature DCs by inhibiting their stimulation by overexpression of TGF-β-produced by regulatory T lymphocytes and stimulation of tumor cells. In addition, the tumor microenvironment stimulated the secretion of cytokines such as IL-10, and CD4 and decreased the secretion of IFN-γ-and IL-12 in tumor-induced mice cultured LN and spleen.</p>\",\"PeriodicalId\":16340,\"journal\":{\"name\":\"Journal of Microscopy and Ultrastructure\",\"volume\":\"11 1\",\"pages\":\"150-160\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-01-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679829/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Microscopy and Ultrastructure\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4103/jmau.jmau_85_22\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/7/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Microscopy and Ultrastructure","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4103/jmau.jmau_85_22","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/7/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
Dendritic Cell-Based Immunity: Screening of Dendritic Cell Subsets in Breast Cancer-Bearing Mice.
Background: Breast cancer (BC) is the most devastating disease, particularly the lethal invasive form. It is the most underlying cause of death among women worldwide. The expansion of BC is controlled by a variety of alterations in the tumor cells themselves, in addition to the state of the immune system, which has a direct influence on the tumor microenvironment. Numerous receptors expressed by T-cells interact with ligands on antigen-presenting cells to provide activation signals results in mounting effector anti-tumor T-cell responses. On the other hand, there is a dearth of information about the actual interactions and reactions of T-cells and dendritic cells (DCs) all through the progression of tumor development.
Aim: Immune system response against BC was investigated through tumor induction in mice. The size and volume of the tumor were calculated. Moreover, the phenotypical profile of T-cells and DCs from lymph nodes (LN) and spleens of BC-bearing mice was investigated. In addition, the levels of Transforming growth factor-β, Interferon-gamma (IFN-γ), Interleukin IL-2, IL-10, IL-4, IL-12, and tumor necrosis factor (TNF)-α were determined.
Materials and methods: MDA231 cells were utilized to induce BC in 30 white BALB/C mice, whereas the other 30 mice acted as healthy controls and were not treated with any cancer-causing agents. The impact of malignancy was evaluated using flow cytometry based on the marking surface molecules, as well as the titer of specific cytokines of the mice's LN culture using the ELISA method. These cytokines included transforming growth factor-β (TGF-β), IFN-γ, IL-2, IL -10, IL -4, IL -12, and TNF-α.
Results: The findings showed that the maturation of DCs was inhibited, followed by an accumulation of immature DCs. These immature DCs increase the release of TGF-β and cytokines like IL-10 and inhibit the release of IFN-γ and IL-12 in the culture supernatant of nodal lymph and spleen suspension of BC-bearing mice compared to control. In addition, there was a low expression of CD80 and CD86 on DCs, which indicates a low maturation process.
Conclusion: According to the findings, the tumor microenvironment may have been responsible for preventing the maturation of DCs. This, in turn, weakened the immune response and facilitated the ability of the tumor to proliferate. Furthermore, the tumor microenvironment increased the number of immature DCs by inhibiting their stimulation by overexpression of TGF-β-produced by regulatory T lymphocytes and stimulation of tumor cells. In addition, the tumor microenvironment stimulated the secretion of cytokines such as IL-10, and CD4 and decreased the secretion of IFN-γ-and IL-12 in tumor-induced mice cultured LN and spleen.