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,...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Afsheen Raza (492657) (author)
مؤلفون آخرون: Reyad Mohsen (14778049) (author), Aladdin Kanbour (14442123) (author), Abdul Rehman Zar Gul (14777347) (author), Anite Philip (14442129) (author), Suma Vijayakumar (14442132) (author), Shereena Hydrose (14442135) (author), Kirti S. Prabhu (4246144) (author), Aisha Khamis Al-Suwaidi (18021682) (author), Varghese Philipose Inchakalody (14153292) (author), Maysaloun Merhi (4246147) (author), Dina M. Abo El-Ella (18021685) (author), Melissa Annrose Tauro (18021688) (author), Shayista Akbar (14442117) (author), Issam Al-Bozom (4711098) (author), Wafa Abualainin (14442141) (author), Rajaa Al-Abdulla (14442138) (author), Shaza Abu Sirriya (18021691) (author), Suparna Hassnad (18021694) (author), Shahab Uddin (154400) (author), Mohamed Izham Mohamed Ibrahim (14158896) (author), Ussama Al Homsi (14442150) (author), Said Demime (18021697) (author)
منشور في: 2023
الموضوعات:
الوسوم: إضافة وسم
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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>
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identifier_str_mv 10.3389/fimmu.2023.1157100
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oai_identifier_str oai:figshare.com:article/25284982
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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