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Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

SIMPLE SUMMARY: Despite the promising results not all patients with advanced non-small cell lung cancer benefit from immunotherapy. Immunotherapy may cause severe adverse events, and therefore, it is important to improve the selection of patients for this treatment. The current biomarker, PD-L1, is...

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Autores principales: Mouritzen, Mette T., Ladekarl, Morten, Hager, Henrik, Mattesen, Trine B., Lippert, Julie B., Frank, Malene S., Nøhr, Anne K., Egendal, Ida B., Carus, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526901/
https://www.ncbi.nlm.nih.gov/pubmed/37760450
http://dx.doi.org/10.3390/cancers15184480
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author Mouritzen, Mette T.
Ladekarl, Morten
Hager, Henrik
Mattesen, Trine B.
Lippert, Julie B.
Frank, Malene S.
Nøhr, Anne K.
Egendal, Ida B.
Carus, Andreas
author_facet Mouritzen, Mette T.
Ladekarl, Morten
Hager, Henrik
Mattesen, Trine B.
Lippert, Julie B.
Frank, Malene S.
Nøhr, Anne K.
Egendal, Ida B.
Carus, Andreas
author_sort Mouritzen, Mette T.
collection PubMed
description SIMPLE SUMMARY: Despite the promising results not all patients with advanced non-small cell lung cancer benefit from immunotherapy. Immunotherapy may cause severe adverse events, and therefore, it is important to improve the selection of patients for this treatment. The current biomarker, PD-L1, is a poor predictive biomarker and complementary biomarkers are warranted. This study aimed to assess the association of gene expressions, blood immune cell counts and clinical characteristics with durable clinical benefit of immunotherapy. The findings of this study may assist in the daily clinical assessment of patients with advanced non-small cell lung cancer, that may be candidates for immunotherapy. Additionally, this study could guide future immunotherapy biomarker studies according to methodology and biomarkers of interest, provided a determined effort to collect sufficient biological material. The assessment of PD-L1 by gene expression profiling and the clinical impact of this method compared to standard immunohistochemistry could also be further explored. ABSTRACT: Background: Not all patients with advanced non-small cell lung cancer (NSCLC) benefit from immune checkpoint inhibitors (ICIs). Therefore, we aimed to assess the predictive potential of gene expression profiling (GEP), peripheral immune cell counts, and clinical characteristics. Methods: The primary endpoint of this prospective, observational study was a durable clinical benefit (DCB) defined as progression-free survival >6 months. In a subgroup with histological biopsies of sufficient quality (n = 25), GEP was performed using the nCounter(®) PanCancer IO 360 panel. Results: DCB was observed in 49% of 123 included patients. High absolute lymphocyte count (ALC) and absence of liver metastases were associated with DCB (OR = 1.95, p = 0.038 and OR = 0.36, p = 0.046, respectively). GEP showed clustering of differentially expressed genes according to DCB, and a strong association between PD-L1 assessed by GEP (CD274) and immunohistochemistry (IHC) was observed (p = 0.00013). The TGF-β, dendritic cell, and myeloid signature scores were higher for patients without DCB, whereas the JAK/STAT loss signature scores were higher for patients with DCB (unadjusted p-values < 0.05). Conclusions: ALC above 1.01 × 10(9)/L and absence of liver metastases were significantly associated with DCB in ICI-treated patients with NSCLC. GEP was only feasible in 20% of the patients. GEP-derived signatures may be associated with clinical outcomes, and PD-L1 could be assessed by GEP rather than IHC.
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spelling pubmed-105269012023-09-28 Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors Mouritzen, Mette T. Ladekarl, Morten Hager, Henrik Mattesen, Trine B. Lippert, Julie B. Frank, Malene S. Nøhr, Anne K. Egendal, Ida B. Carus, Andreas Cancers (Basel) Article SIMPLE SUMMARY: Despite the promising results not all patients with advanced non-small cell lung cancer benefit from immunotherapy. Immunotherapy may cause severe adverse events, and therefore, it is important to improve the selection of patients for this treatment. The current biomarker, PD-L1, is a poor predictive biomarker and complementary biomarkers are warranted. This study aimed to assess the association of gene expressions, blood immune cell counts and clinical characteristics with durable clinical benefit of immunotherapy. The findings of this study may assist in the daily clinical assessment of patients with advanced non-small cell lung cancer, that may be candidates for immunotherapy. Additionally, this study could guide future immunotherapy biomarker studies according to methodology and biomarkers of interest, provided a determined effort to collect sufficient biological material. The assessment of PD-L1 by gene expression profiling and the clinical impact of this method compared to standard immunohistochemistry could also be further explored. ABSTRACT: Background: Not all patients with advanced non-small cell lung cancer (NSCLC) benefit from immune checkpoint inhibitors (ICIs). Therefore, we aimed to assess the predictive potential of gene expression profiling (GEP), peripheral immune cell counts, and clinical characteristics. Methods: The primary endpoint of this prospective, observational study was a durable clinical benefit (DCB) defined as progression-free survival >6 months. In a subgroup with histological biopsies of sufficient quality (n = 25), GEP was performed using the nCounter(®) PanCancer IO 360 panel. Results: DCB was observed in 49% of 123 included patients. High absolute lymphocyte count (ALC) and absence of liver metastases were associated with DCB (OR = 1.95, p = 0.038 and OR = 0.36, p = 0.046, respectively). GEP showed clustering of differentially expressed genes according to DCB, and a strong association between PD-L1 assessed by GEP (CD274) and immunohistochemistry (IHC) was observed (p = 0.00013). The TGF-β, dendritic cell, and myeloid signature scores were higher for patients without DCB, whereas the JAK/STAT loss signature scores were higher for patients with DCB (unadjusted p-values < 0.05). Conclusions: ALC above 1.01 × 10(9)/L and absence of liver metastases were significantly associated with DCB in ICI-treated patients with NSCLC. GEP was only feasible in 20% of the patients. GEP-derived signatures may be associated with clinical outcomes, and PD-L1 could be assessed by GEP rather than IHC. MDPI 2023-09-08 /pmc/articles/PMC10526901/ /pubmed/37760450 http://dx.doi.org/10.3390/cancers15184480 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mouritzen, Mette T.
Ladekarl, Morten
Hager, Henrik
Mattesen, Trine B.
Lippert, Julie B.
Frank, Malene S.
Nøhr, Anne K.
Egendal, Ida B.
Carus, Andreas
Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors
title Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors
title_full Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors
title_fullStr Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors
title_full_unstemmed Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors
title_short Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors
title_sort gene expressions and high lymphocyte count may predict durable clinical benefits in patients with advanced non-small-cell lung cancer treated with immune checkpoint inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526901/
https://www.ncbi.nlm.nih.gov/pubmed/37760450
http://dx.doi.org/10.3390/cancers15184480
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