Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression
<p dir="ltr">Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes with better overall survival,...
محفوظ في:
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| مؤلفون آخرون: | , , , , , , , , , , , , , , , , , , , , , |
| منشور في: |
2023
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إضافة وسم
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| _version_ | 1864513526456909824 |
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| author | Afsheen Raza (492657) |
| author2 | Reyad Mohsen (14778049) Aladdin Kanbour (14442123) Abdul Rehman Zar Gul (14777347) Anite Philip (14442129) Suma Vijayakumar (14442132) Shereena Hydrose (14442135) Kirti S. Prabhu (4246144) Aisha Khamis Al-Suwaidi (18021682) Varghese Philipose Inchakalody (14153292) Maysaloun Merhi (4246147) Dina M. Abo El-Ella (18021685) Melissa Annrose Tauro (18021688) Shayista Akbar (14442117) Issam Al-Bozom (4711098) Wafa Abualainin (14442141) Rajaa Al-Abdulla (14442138) Shaza Abu Sirriya (18021691) Suparna Hassnad (18021694) Shahab Uddin (154400) Mohamed Izham Mohamed Ibrahim (14158896) Ussama Al Homsi (14442150) Said Demime (18021697) |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Afsheen Raza (492657) Reyad Mohsen (14778049) Aladdin Kanbour (14442123) Abdul Rehman Zar Gul (14777347) Anite Philip (14442129) Suma Vijayakumar (14442132) Shereena Hydrose (14442135) Kirti S. Prabhu (4246144) Aisha Khamis Al-Suwaidi (18021682) Varghese Philipose Inchakalody (14153292) Maysaloun Merhi (4246147) Dina M. Abo El-Ella (18021685) Melissa Annrose Tauro (18021688) Shayista Akbar (14442117) Issam Al-Bozom (4711098) Wafa Abualainin (14442141) Rajaa Al-Abdulla (14442138) Shaza Abu Sirriya (18021691) Suparna Hassnad (18021694) Shahab Uddin (154400) Mohamed Izham Mohamed Ibrahim (14158896) Ussama Al Homsi (14442150) Said Demime (18021697) |
| author_role | author |
| dc.creator.none.fl_str_mv | Afsheen Raza (492657) Reyad Mohsen (14778049) Aladdin Kanbour (14442123) Abdul Rehman Zar Gul (14777347) Anite Philip (14442129) Suma Vijayakumar (14442132) Shereena Hydrose (14442135) Kirti S. Prabhu (4246144) Aisha Khamis Al-Suwaidi (18021682) Varghese Philipose Inchakalody (14153292) Maysaloun Merhi (4246147) Dina M. Abo El-Ella (18021685) Melissa Annrose Tauro (18021688) Shayista Akbar (14442117) Issam Al-Bozom (4711098) Wafa Abualainin (14442141) Rajaa Al-Abdulla (14442138) Shaza Abu Sirriya (18021691) Suparna Hassnad (18021694) Shahab Uddin (154400) Mohamed Izham Mohamed Ibrahim (14158896) Ussama Al Homsi (14442150) Said Demime (18021697) |
| dc.date.none.fl_str_mv | 2023-05-15T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fimmu.2023.1157100 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Serum_immune_mediators_as_novel_predictors_of_response_to_anti-PD-1_PD-L1_therapy_in_non-small_cell_lung_cancer_patients_with_high_tissue-PD-L1_expression/25284982 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology Oncology and carcinogenesis non-small cell lung cancer anti-PD-1 anti-PD-L1 tissue PD-L1 predictive soluble biomarkers CEA |
| dc.title.none.fl_str_mv | Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes with better overall survival, but only 15-40% of the patients respond to ICIs therapy. The search for predictive biomarkers of responses is warranted for better clinical outcomes. We aim here to identify pre-treatment soluble immune molecules as surrogate biomarkers for tissue PD-L1 (TPD-L1) status and as predictors of response to anti-PD-1/PD-L1 therapy in NSCLC patients. Sera from 31 metastatic NSCLC patients, eligible for anti-PD-1/PD-L1 or combined chemoimmunotherapy, were collected prior to treatment. Analysis of soluble biomarkers with TPD-L1 status showed significant up/down regulation of the immune inhibitory checkpoint markers (sSiglec7, sSiglec9, sULBP4 and sPD-L2) in patients with higher TPD-L1 (TPD-L1 >50%) expression. Moreover, correlation analysis showed significant positive linear correlation of soluble PD-L1 (sPD-L1) with higher TPD-L1 expression. Interestingly, only responders in the TPD-L1 >50% group showed significant down regulation of the immune inhibitory markers (sPD-L2, sTIMD4, sNectin2 and CEA). When responders vs. non-responders were compared, significant down regulation of other immune inhibitory biomarkers (sCD80, sTIMD4 and CEA) was recorded only in responding patients. In this, the optimal cut-off values of CD80 <91.7 pg/ml and CEA <1614 pg/ml were found to be significantly associated with better progression free survival (PFS). Indeed, multivariate analysis identified the cutoff-value of CEA <1614 pg/ml as an independent predictor of response in our patients. We identified here novel immune inhibitory/stimulatory soluble mediators as potential surrogate/predictive biomarkers for TPD-L1 status, treatment response and PFS in NSCLC patients treated with anti-PD-1/PD-L1 therapy.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Immunology<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/10.3389/fimmu.2023.1157100" target="_blank">https://dx.doi.org/10.3389/fimmu.2023.1157100</a></p><p dir="ltr">Additional institutions affiliated with: Academic Health System - HMC and Qatar University Health - QU</p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_e390cb9db2a7e99bc6039db8470ac65c |
| identifier_str_mv | 10.3389/fimmu.2023.1157100 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25284982 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expressionAfsheen Raza (492657)Reyad Mohsen (14778049)Aladdin Kanbour (14442123)Abdul Rehman Zar Gul (14777347)Anite Philip (14442129)Suma Vijayakumar (14442132)Shereena Hydrose (14442135)Kirti S. Prabhu (4246144)Aisha Khamis Al-Suwaidi (18021682)Varghese Philipose Inchakalody (14153292)Maysaloun Merhi (4246147)Dina M. Abo El-Ella (18021685)Melissa Annrose Tauro (18021688)Shayista Akbar (14442117)Issam Al-Bozom (4711098)Wafa Abualainin (14442141)Rajaa Al-Abdulla (14442138)Shaza Abu Sirriya (18021691)Suparna Hassnad (18021694)Shahab Uddin (154400)Mohamed Izham Mohamed Ibrahim (14158896)Ussama Al Homsi (14442150)Said Demime (18021697)Biomedical and clinical sciencesImmunologyOncology and carcinogenesisnon-small cell lung canceranti-PD-1anti-PD-L1tissue PD-L1predictive soluble biomarkersCEA<p dir="ltr">Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes with better overall survival, but only 15-40% of the patients respond to ICIs therapy. The search for predictive biomarkers of responses is warranted for better clinical outcomes. We aim here to identify pre-treatment soluble immune molecules as surrogate biomarkers for tissue PD-L1 (TPD-L1) status and as predictors of response to anti-PD-1/PD-L1 therapy in NSCLC patients. Sera from 31 metastatic NSCLC patients, eligible for anti-PD-1/PD-L1 or combined chemoimmunotherapy, were collected prior to treatment. Analysis of soluble biomarkers with TPD-L1 status showed significant up/down regulation of the immune inhibitory checkpoint markers (sSiglec7, sSiglec9, sULBP4 and sPD-L2) in patients with higher TPD-L1 (TPD-L1 >50%) expression. Moreover, correlation analysis showed significant positive linear correlation of soluble PD-L1 (sPD-L1) with higher TPD-L1 expression. Interestingly, only responders in the TPD-L1 >50% group showed significant down regulation of the immune inhibitory markers (sPD-L2, sTIMD4, sNectin2 and CEA). When responders vs. non-responders were compared, significant down regulation of other immune inhibitory biomarkers (sCD80, sTIMD4 and CEA) was recorded only in responding patients. In this, the optimal cut-off values of CD80 <91.7 pg/ml and CEA <1614 pg/ml were found to be significantly associated with better progression free survival (PFS). Indeed, multivariate analysis identified the cutoff-value of CEA <1614 pg/ml as an independent predictor of response in our patients. We identified here novel immune inhibitory/stimulatory soluble mediators as potential surrogate/predictive biomarkers for TPD-L1 status, treatment response and PFS in NSCLC patients treated with anti-PD-1/PD-L1 therapy.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Immunology<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/10.3389/fimmu.2023.1157100" target="_blank">https://dx.doi.org/10.3389/fimmu.2023.1157100</a></p><p dir="ltr">Additional institutions affiliated with: Academic Health System - HMC and Qatar University Health - QU</p>2023-05-15T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fimmu.2023.1157100https://figshare.com/articles/journal_contribution/Serum_immune_mediators_as_novel_predictors_of_response_to_anti-PD-1_PD-L1_therapy_in_non-small_cell_lung_cancer_patients_with_high_tissue-PD-L1_expression/25284982CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/252849822023-05-15T03:00:00Z |
| spellingShingle | Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression Afsheen Raza (492657) Biomedical and clinical sciences Immunology Oncology and carcinogenesis non-small cell lung cancer anti-PD-1 anti-PD-L1 tissue PD-L1 predictive soluble biomarkers CEA |
| status_str | publishedVersion |
| title | Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression |
| title_full | Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression |
| title_fullStr | Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression |
| title_full_unstemmed | Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression |
| title_short | Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression |
| title_sort | Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression |
| topic | Biomedical and clinical sciences Immunology Oncology and carcinogenesis non-small cell lung cancer anti-PD-1 anti-PD-L1 tissue PD-L1 predictive soluble biomarkers CEA |