Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy
<h2>Background</h2><p dir="ltr">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...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , , , , , , , , , |
| منشور في: |
2023
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| الموضوعات: | |
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إضافة وسم
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| _version_ | 1864513533075521536 |
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| author | Nassiba Taib (14557385) |
| author2 | Maysaloun Merhi (4246147) Varghese Inchakalody (15263530) Sarra Mestiri (14557379) Shereena Hydrose (14442135) Karama Makni-Maalej (15263533) Afsheen Raza (492657) Fairooz Sahir (6595517) Fouad Azizi (11835843) Parveen B. Nizamuddin (14590613) Queenie Fernandes (14557388) Zeenath Safira K. M. Yoosuf (15263536) Salam Almoghrabi (15263539) Lobna Al-Zaidan (14557394) Alaaeldin Shablak (14778097) Shahab Uddin (154400) Cristina Maccalli (2632465) Mohammed Ussama Al Homsi (15263542) Said Dermime (79420) |
| author2_role | author author author author author author author author author author author author author author author author author author |
| author_facet | Nassiba Taib (14557385) Maysaloun Merhi (4246147) Varghese Inchakalody (15263530) Sarra Mestiri (14557379) Shereena Hydrose (14442135) Karama Makni-Maalej (15263533) Afsheen Raza (492657) Fairooz Sahir (6595517) Fouad Azizi (11835843) Parveen B. Nizamuddin (14590613) Queenie Fernandes (14557388) Zeenath Safira K. M. Yoosuf (15263536) Salam Almoghrabi (15263539) Lobna Al-Zaidan (14557394) Alaaeldin Shablak (14778097) Shahab Uddin (154400) Cristina Maccalli (2632465) Mohammed Ussama Al Homsi (15263542) Said Dermime (79420) |
| author_role | author |
| dc.creator.none.fl_str_mv | Nassiba Taib (14557385) Maysaloun Merhi (4246147) Varghese Inchakalody (15263530) Sarra Mestiri (14557379) Shereena Hydrose (14442135) Karama Makni-Maalej (15263533) Afsheen Raza (492657) Fairooz Sahir (6595517) Fouad Azizi (11835843) Parveen B. Nizamuddin (14590613) Queenie Fernandes (14557388) Zeenath Safira K. M. Yoosuf (15263536) Salam Almoghrabi (15263539) Lobna Al-Zaidan (14557394) Alaaeldin Shablak (14778097) Shahab Uddin (154400) Cristina Maccalli (2632465) Mohammed Ussama Al Homsi (15263542) Said Dermime (79420) |
| dc.date.none.fl_str_mv | 2023-03-31T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s12967-023-04073-y |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Treatment_with_decitabine_induces_the_expression_of_stemness_markers_PD-L1_and_NY-ESO-1_in_colorectal_cancer_potential_for_combined_chemoimmunotherapy/24941844 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Reproductive medicine Colorectal cancer Decitabine NY-ESO-1 PD-L1 Stemness markers Chemoresistance Immune escape |
| dc.title.none.fl_str_mv | Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h2>Background</h2><p dir="ltr">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.</p><h2>Methods</h2><p dir="ltr">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.</p><h2>Results</h2><p dir="ltr">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.</p><h2>Conclusions</h2><p dir="ltr">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.</p><p dir="ltr"><br></p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Translational Medicine<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12967-023-04073-y" target="_blank">https://dx.doi.org/10.1186/s12967-023-04073-y</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_54849e8a3be3e0c5634223c11eb140cf |
| identifier_str_mv | 10.1186/s12967-023-04073-y |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/24941844 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapyNassiba Taib (14557385)Maysaloun Merhi (4246147)Varghese Inchakalody (15263530)Sarra Mestiri (14557379)Shereena Hydrose (14442135)Karama Makni-Maalej (15263533)Afsheen Raza (492657)Fairooz Sahir (6595517)Fouad Azizi (11835843)Parveen B. Nizamuddin (14590613)Queenie Fernandes (14557388)Zeenath Safira K. M. Yoosuf (15263536)Salam Almoghrabi (15263539)Lobna Al-Zaidan (14557394)Alaaeldin Shablak (14778097)Shahab Uddin (154400)Cristina Maccalli (2632465)Mohammed Ussama Al Homsi (15263542)Said Dermime (79420)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesReproductive medicineColorectal cancerDecitabineNY-ESO-1PD-L1Stemness markersChemoresistanceImmune escape<h2>Background</h2><p dir="ltr">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.</p><h2>Methods</h2><p dir="ltr">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.</p><h2>Results</h2><p dir="ltr">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.</p><h2>Conclusions</h2><p dir="ltr">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.</p><p dir="ltr"><br></p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Translational Medicine<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12967-023-04073-y" target="_blank">https://dx.doi.org/10.1186/s12967-023-04073-y</a></p>2023-03-31T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12967-023-04073-yhttps://figshare.com/articles/journal_contribution/Treatment_with_decitabine_induces_the_expression_of_stemness_markers_PD-L1_and_NY-ESO-1_in_colorectal_cancer_potential_for_combined_chemoimmunotherapy/24941844CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/249418442023-03-31T03:00:00Z |
| spellingShingle | Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy Nassiba Taib (14557385) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Reproductive medicine Colorectal cancer Decitabine NY-ESO-1 PD-L1 Stemness markers Chemoresistance Immune escape |
| status_str | publishedVersion |
| title | Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy |
| title_full | Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy |
| title_fullStr | Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy |
| title_full_unstemmed | Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy |
| title_short | Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy |
| title_sort | Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Reproductive medicine Colorectal cancer Decitabine NY-ESO-1 PD-L1 Stemness markers Chemoresistance Immune escape |