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iNOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer
SIMPLE SUMMARY: The role of Inducible Nitric Oxygen Synthase (iNOS) in the progression of human malignancies is obscure. We studied the expression patterns of iNOS in non-small-cell lung cancer. iNOS was expressed by cancer cells and cancer-associated fibroblasts. None of these patterns, however, ar...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694334/ https://www.ncbi.nlm.nih.gov/pubmed/33167430 http://dx.doi.org/10.3390/cancers12113276 |
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author | Giatromanolaki, Alexandra Tsolou, Avgi Daridou, Eleftheria Kouroupi, Maria Chlichlia, Katerina Koukourakis, Michael I. |
author_facet | Giatromanolaki, Alexandra Tsolou, Avgi Daridou, Eleftheria Kouroupi, Maria Chlichlia, Katerina Koukourakis, Michael I. |
author_sort | Giatromanolaki, Alexandra |
collection | PubMed |
description | SIMPLE SUMMARY: The role of Inducible Nitric Oxygen Synthase (iNOS) in the progression of human malignancies is obscure. We studied the expression patterns of iNOS in non-small-cell lung cancer. iNOS was expressed by cancer cells and cancer-associated fibroblasts. None of these patterns, however, are related to stage or prognosis. Extensive infiltration of the tumor stroma by iNOS-expressing tumor-infiltrating lymphocytes ((iNOS+)TILs) occurred in 48% of cases. This was related to low Hypoxia-Inducible Factor 1α (HIF1α) and better overall survival. Expression of Programmed death-ligand 1 PD-L1, however, mitigates the beneficial effect of the presence of (iNOS+)TIL. An important role of iNOS in anti-neoplastic lymphocyte biology has been brought forward, supporting (iNOS+)TILs as putative immune response markers. ABSTRACT: Background: Inducible Nitric Oxygen Synthase (iNOS) promotes the generation of NO in tissues. Its role in tumor progression and immune response is unclear. Methods: The immunohistochemical expression patterns of iNOS were studied in a series of 98 tissue samples of non-small-cell lung carcinoma (NSCLC), in parallel with the expression of hypoxia and anaerobic metabolism markers, PD-L1 and tumor-infiltrating lymphocytes (TILs). Results: iNOS is expressed by cancer cells in 19/98 (19.4%), while extensive expression by cancer-associated fibroblasts occurs in 8/98 (8.2%) cases. None of these patterns relate to stage or prognosis. Extensive infiltration of the tumor stroma by iNOS-expressing TILs ((iNOS+)TILs) occurs in 47/98 (48%) cases. This is related to low Hypoxia-Inducible Factor 1α (HIF1α), high PD-L1 expression and a better overall survival (p = 0.002). Expression of PD-L1, however, mitigates the beneficial effect of the presence of (iNOS+)TIL. Conclusions: Extensive expression of iNOS by TILs occurs in approximately 50% of NSCLCs, and this is significantly related to an improved overall survival. This brings forward the role of iNOS in anti-neoplastic lymphocyte biology, supporting (iNOS+)TILs as a putative marker of immune response. The value of this biomarker as a predictive and treatment-guiding tool for tumor immunotherapy demands further investigation. |
format | Online Article Text |
id | pubmed-7694334 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76943342020-11-28 iNOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer Giatromanolaki, Alexandra Tsolou, Avgi Daridou, Eleftheria Kouroupi, Maria Chlichlia, Katerina Koukourakis, Michael I. Cancers (Basel) Article SIMPLE SUMMARY: The role of Inducible Nitric Oxygen Synthase (iNOS) in the progression of human malignancies is obscure. We studied the expression patterns of iNOS in non-small-cell lung cancer. iNOS was expressed by cancer cells and cancer-associated fibroblasts. None of these patterns, however, are related to stage or prognosis. Extensive infiltration of the tumor stroma by iNOS-expressing tumor-infiltrating lymphocytes ((iNOS+)TILs) occurred in 48% of cases. This was related to low Hypoxia-Inducible Factor 1α (HIF1α) and better overall survival. Expression of Programmed death-ligand 1 PD-L1, however, mitigates the beneficial effect of the presence of (iNOS+)TIL. An important role of iNOS in anti-neoplastic lymphocyte biology has been brought forward, supporting (iNOS+)TILs as putative immune response markers. ABSTRACT: Background: Inducible Nitric Oxygen Synthase (iNOS) promotes the generation of NO in tissues. Its role in tumor progression and immune response is unclear. Methods: The immunohistochemical expression patterns of iNOS were studied in a series of 98 tissue samples of non-small-cell lung carcinoma (NSCLC), in parallel with the expression of hypoxia and anaerobic metabolism markers, PD-L1 and tumor-infiltrating lymphocytes (TILs). Results: iNOS is expressed by cancer cells in 19/98 (19.4%), while extensive expression by cancer-associated fibroblasts occurs in 8/98 (8.2%) cases. None of these patterns relate to stage or prognosis. Extensive infiltration of the tumor stroma by iNOS-expressing TILs ((iNOS+)TILs) occurs in 47/98 (48%) cases. This is related to low Hypoxia-Inducible Factor 1α (HIF1α), high PD-L1 expression and a better overall survival (p = 0.002). Expression of PD-L1, however, mitigates the beneficial effect of the presence of (iNOS+)TIL. Conclusions: Extensive expression of iNOS by TILs occurs in approximately 50% of NSCLCs, and this is significantly related to an improved overall survival. This brings forward the role of iNOS in anti-neoplastic lymphocyte biology, supporting (iNOS+)TILs as a putative marker of immune response. The value of this biomarker as a predictive and treatment-guiding tool for tumor immunotherapy demands further investigation. MDPI 2020-11-05 /pmc/articles/PMC7694334/ /pubmed/33167430 http://dx.doi.org/10.3390/cancers12113276 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Giatromanolaki, Alexandra Tsolou, Avgi Daridou, Eleftheria Kouroupi, Maria Chlichlia, Katerina Koukourakis, Michael I. iNOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer |
title | iNOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer |
title_full | iNOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer |
title_fullStr | iNOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer |
title_full_unstemmed | iNOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer |
title_short | iNOS Expression by Tumor-Infiltrating Lymphocytes, PD-L1 and Prognosis in Non-Small-Cell Lung Cancer |
title_sort | inos expression by tumor-infiltrating lymphocytes, pd-l1 and prognosis in non-small-cell lung cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694334/ https://www.ncbi.nlm.nih.gov/pubmed/33167430 http://dx.doi.org/10.3390/cancers12113276 |
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