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المؤلفTaib, Nassiba
المؤلفMerhi, Maysaloun
المؤلفInchakalody, Varghese
المؤلفMestiri, Sarra
المؤلفHydrose, Shereena
المؤلفMakni-Maalej, Karama
المؤلفRaza, Afsheen
المؤلفSahir, Fairooz
المؤلفAzizi, Fouad
المؤلفNizamuddin, Parveen B.
المؤلفFernandes, Queenie
المؤلفYoosuf, Zeenath Safira K. M.
المؤلفAlmoghrabi, Salam
المؤلفAl-Zaidan, Lobna
المؤلفShablak, Alaaeldin
المؤلفUddin, Shahab
المؤلفMaccalli, Cristina
المؤلفAl Homsi, Mohammed Ussama
المؤلفDermime, Said
تاريخ الإتاحة2023-05-15T06:13:55Z
تاريخ النشر2023
اسم المنشورJournal of Translational Medicine
المصدرScopus
الرقم المعياري الدولي للكتاب1479-5876
معرّف المصادر الموحدhttp://dx.doi.org/10.1186/s12967-023-04073-y
معرّف المصادر الموحدhttp://hdl.handle.net/10576/42696
الملخصBackground: The mechanism of tumor immune escape and progression in colorectal cancer (CRC) is widely investigated in-vitro to help understand and identify agents that might play a crucial role in response to treatment and improve the overall survival of CRC patients. Several mechanisms of immune escape and tumor progression, including expression of stemness markers, inactivation of immunoregulatory genes by methylation, and epigenetic silencing, have been reported in CRC, indicating the potential of demethylating agents as anti-cancer drugs. Of these, a chemotherapeutic demethylating agent, Decitabine (DAC), has been reported to induce a dual effect on both DNA demethylation and histone changes leading to an increased expression of target biomarkers, thus making it an attractive anti-tumorigenic drug. Methods: We compared the effect of DAC in primary 1076 Col and metastatic 1872 Col cell lines isolated and generated from patients' tumor tissues. Both cell lines were treated with DAC, and the expression of the NY-ESO-1 cancer-testis antigen, the PD-L1 immunoinhibitory marker, and the CD44, Nanog, KLF-4, CD133, MSI-1 stemness markers were analyzed using different molecular and immunological assays. Results: DAC treatment significantly upregulated stemness markers in both primary 1076 Col and meta-static 1872 Col cell lines, although a lower effect occurred on the latter: CD44 (7.85 fold; ***p = 0.0001 vs. (4.19 fold; *p = 0.0120), Nanog (4.1 fold; ***p < 0.0001 vs.1.69 fold; ***p = 0.0008), KLF-4 (4.33 fold; ***p < 0.0001 vs.2.48 fold; ***p = 0.0005), CD133 (16.77 fold; ***p = 0.0003 vs.6.36 fold; *p = 0.0166), and MSI-1 (2.33 fold; ***p = 0.0003 vs.2.3 fold; ***p = 0.0004), respectively. Interestingly, in the metastatic 1872 Col cells treated with DAC, the expression of both PD-L1 and NY-ESO-1 was increased tenfold (*p = 0.0128) and fivefold (***p < 0.0001), respectively. Conclusions: We conclude that the upregulation of both stemness and immune checkpoint markers by DAC treatment on CRC cells might represent a mechanism of immune evasion. In addition, induction of NY-ESO-1 may represent an immuno-therapeutic option in metastatic CRC patients. Finally, the combination of DAC and anti-PD-1/anti-PD-L1 antibodies treatment should represent a potential therapeutic intervention for this group of patients. 2023, The Author(s).
راعي المشروعOpen Access funding provided by the Qatar National Library. The study was supported by the Medical Research Center, Academic Health System, at Hamad Medical Corporation as part of the approved funded IRGC project # IRGC-04-SI-17-142. The Open Access funding is provided by Qatar National Library, Doha, Qatar.
اللغةen
الناشرBioMed Central Ltd
الموضوعChemoresistance; Colorectal cancer; Decitabine; Immune escape; NY-ESO-1; PD-L1; Stemness markers
العنوانTreatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy
النوعArticle
رقم العدد1
رقم المجلد21
dc.accessType Open Access


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