Systems Immunology Analysis Reveals an Immunomodulatory Effect of Snail-p53 Binding on Neutrophil- and T Cell-Mediated Immunity in KRAS Mutant Non-Small Cell Lung Cancer
Immunomodulation and chronic inflammation are important mechanisms utilized by cancer cells to evade the immune defense and promote tumor progression. Therefore, various efforts were focused on the development of approaches to reprogram the immune response to increase the immune detection of cancer...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.569671/full |
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| author | Sarah Musa Hammoudeh Sarah Musa Hammoudeh Thenmozhi Venkatachalam Abdul Wahid Ansari Riyad Bendardaf Riyad Bendardaf Qutayba Hamid Qutayba Hamid Mohamed Rahmani Mohamed Rahmani Rifat Hamoudi Rifat Hamoudi Rifat Hamoudi |
| author_facet | Sarah Musa Hammoudeh Sarah Musa Hammoudeh Thenmozhi Venkatachalam Abdul Wahid Ansari Riyad Bendardaf Riyad Bendardaf Qutayba Hamid Qutayba Hamid Mohamed Rahmani Mohamed Rahmani Rifat Hamoudi Rifat Hamoudi Rifat Hamoudi |
| author_sort | Sarah Musa Hammoudeh |
| collection | DOAJ |
| description | Immunomodulation and chronic inflammation are important mechanisms utilized by cancer cells to evade the immune defense and promote tumor progression. Therefore, various efforts were focused on the development of approaches to reprogram the immune response to increase the immune detection of cancer cells and enhance patient response to various types of therapy. A number of regulatory proteins were investigated and proposed as potential targets for immunomodulatory therapeutic approaches including p53 and Snail. In this study, we investigated the immunomodulatory effect of disrupting Snail-p53 binding induced by the oncogenic KRAS to suppress p53 signaling. We analyzed the transcriptomic profile mediated by Snail-p53 binding inhibitor GN25 in non-small cell lung cancer cells (A549) using Next generation whole RNA-sequencing. Notably, we observed a significant enrichment in transcripts involved in immune response pathways especially those contributing to neutrophil (IL8) and T-cell mediated immunity (BCL6, and CD81). Moreover, transcripts associated with NF-κB signaling were also enriched which may play an important role in the immunomodulatory effect of Snail-p53 binding. Further analysis revealed that the immune expression signature of GN25 overlaps with the signature of other therapeutic compounds known to exhibit immunomodulatory effects validating the immunomodulatory potential of targeting Snail-p53 binding. The effects of GN25 on the immune response pathways suggest that targeting Snail-p53 binding might be a potentially effective therapeutic strategy. |
| first_indexed | 2024-12-14T05:13:26Z |
| format | Article |
| id | doaj.art-9e56996953224533843c078078bcdefb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T05:13:26Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9e56996953224533843c078078bcdefb2022-12-21T23:15:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-12-011110.3389/fimmu.2020.569671569671Systems Immunology Analysis Reveals an Immunomodulatory Effect of Snail-p53 Binding on Neutrophil- and T Cell-Mediated Immunity in KRAS Mutant Non-Small Cell Lung CancerSarah Musa Hammoudeh0Sarah Musa Hammoudeh1Thenmozhi Venkatachalam2Abdul Wahid Ansari3Riyad Bendardaf4Riyad Bendardaf5Qutayba Hamid6Qutayba Hamid7Mohamed Rahmani8Mohamed Rahmani9Rifat Hamoudi10Rifat Hamoudi11Rifat Hamoudi12Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesClinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesOncology Unit, University Hospital Sharjah, Sharjah, United Arab EmiratesClinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesMeakins-Christie Laboratories, McGill University, Montreal, QC, CanadaClinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesClinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesDivision of Surgery and Interventional Science, University College London, London, United KingdomImmunomodulation and chronic inflammation are important mechanisms utilized by cancer cells to evade the immune defense and promote tumor progression. Therefore, various efforts were focused on the development of approaches to reprogram the immune response to increase the immune detection of cancer cells and enhance patient response to various types of therapy. A number of regulatory proteins were investigated and proposed as potential targets for immunomodulatory therapeutic approaches including p53 and Snail. In this study, we investigated the immunomodulatory effect of disrupting Snail-p53 binding induced by the oncogenic KRAS to suppress p53 signaling. We analyzed the transcriptomic profile mediated by Snail-p53 binding inhibitor GN25 in non-small cell lung cancer cells (A549) using Next generation whole RNA-sequencing. Notably, we observed a significant enrichment in transcripts involved in immune response pathways especially those contributing to neutrophil (IL8) and T-cell mediated immunity (BCL6, and CD81). Moreover, transcripts associated with NF-κB signaling were also enriched which may play an important role in the immunomodulatory effect of Snail-p53 binding. Further analysis revealed that the immune expression signature of GN25 overlaps with the signature of other therapeutic compounds known to exhibit immunomodulatory effects validating the immunomodulatory potential of targeting Snail-p53 binding. The effects of GN25 on the immune response pathways suggest that targeting Snail-p53 binding might be a potentially effective therapeutic strategy.https://www.frontiersin.org/articles/10.3389/fimmu.2020.569671/fullimmunomodulationsnail-p53 bindingnon-small cell lung cancerT-cell mediated anticancer immunityneutrophil-mediated anticancer immunitysystems immunology |
| spellingShingle | Sarah Musa Hammoudeh Sarah Musa Hammoudeh Thenmozhi Venkatachalam Abdul Wahid Ansari Riyad Bendardaf Riyad Bendardaf Qutayba Hamid Qutayba Hamid Mohamed Rahmani Mohamed Rahmani Rifat Hamoudi Rifat Hamoudi Rifat Hamoudi Systems Immunology Analysis Reveals an Immunomodulatory Effect of Snail-p53 Binding on Neutrophil- and T Cell-Mediated Immunity in KRAS Mutant Non-Small Cell Lung Cancer Frontiers in Immunology immunomodulation snail-p53 binding non-small cell lung cancer T-cell mediated anticancer immunity neutrophil-mediated anticancer immunity systems immunology |
| title | Systems Immunology Analysis Reveals an Immunomodulatory Effect of Snail-p53 Binding on Neutrophil- and T Cell-Mediated Immunity in KRAS Mutant Non-Small Cell Lung Cancer |
| title_full | Systems Immunology Analysis Reveals an Immunomodulatory Effect of Snail-p53 Binding on Neutrophil- and T Cell-Mediated Immunity in KRAS Mutant Non-Small Cell Lung Cancer |
| title_fullStr | Systems Immunology Analysis Reveals an Immunomodulatory Effect of Snail-p53 Binding on Neutrophil- and T Cell-Mediated Immunity in KRAS Mutant Non-Small Cell Lung Cancer |
| title_full_unstemmed | Systems Immunology Analysis Reveals an Immunomodulatory Effect of Snail-p53 Binding on Neutrophil- and T Cell-Mediated Immunity in KRAS Mutant Non-Small Cell Lung Cancer |
| title_short | Systems Immunology Analysis Reveals an Immunomodulatory Effect of Snail-p53 Binding on Neutrophil- and T Cell-Mediated Immunity in KRAS Mutant Non-Small Cell Lung Cancer |
| title_sort | systems immunology analysis reveals an immunomodulatory effect of snail p53 binding on neutrophil and t cell mediated immunity in kras mutant non small cell lung cancer |
| topic | immunomodulation snail-p53 binding non-small cell lung cancer T-cell mediated anticancer immunity neutrophil-mediated anticancer immunity systems immunology |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.569671/full |
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