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Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy?

Multiple studies demonstrate significantly better therapeutics outcomes in smokers as compared with never smokers when single-agent immunotherapy is applied. Non-smoker patients usually need a combination of chemoimmunotherapy to achieve comparable or slightly better therapeutic results. This effect...

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Autores principales: Zaleskis, Gintaras, Pasukoniene, Vita, Characiejus, Dainius, Urbonas, Vincas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378371/
https://www.ncbi.nlm.nih.gov/pubmed/34413168
http://dx.doi.org/10.1136/jitc-2021-003191
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author Zaleskis, Gintaras
Pasukoniene, Vita
Characiejus, Dainius
Urbonas, Vincas
author_facet Zaleskis, Gintaras
Pasukoniene, Vita
Characiejus, Dainius
Urbonas, Vincas
author_sort Zaleskis, Gintaras
collection PubMed
description Multiple studies demonstrate significantly better therapeutics outcomes in smokers as compared with never smokers when single-agent immunotherapy is applied. Non-smoker patients usually need a combination of chemoimmunotherapy to achieve comparable or slightly better therapeutic results. This effect is thought to be due to tobacco product-induced upregulation of PD-L1/PD-1 expression and tumor mutational burden score. Genomic transformation, however, cannot entirely explain the upregulation of PD-L1/PL-1 expression in cells following short-term exposure to cytotoxic compounds. Cytotoxic drugs, crude tobacco products, benzo(a)pyrene, nicotine, and multiple other toxic compounds were shown to exhibit rapid PD-L1/PD-1 upregulation. A significant immunomodulatory effect of nicotine via acetylcholine receptors is well documented. However, nicotine activity rapidly subsides when the drug is withdrawn. We hypothesize that smoking cessation might mitigate the benefits of monoimmunotherapy for some patients. Further studies of the nicotinic acetylcholine receptor stimulus of immunocytes are needed and might lead to characterization and clinical implementation of new immunotherapy sensitizer products.
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spelling pubmed-83783712021-09-02 Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy? Zaleskis, Gintaras Pasukoniene, Vita Characiejus, Dainius Urbonas, Vincas J Immunother Cancer Hypothesis Multiple studies demonstrate significantly better therapeutics outcomes in smokers as compared with never smokers when single-agent immunotherapy is applied. Non-smoker patients usually need a combination of chemoimmunotherapy to achieve comparable or slightly better therapeutic results. This effect is thought to be due to tobacco product-induced upregulation of PD-L1/PD-1 expression and tumor mutational burden score. Genomic transformation, however, cannot entirely explain the upregulation of PD-L1/PL-1 expression in cells following short-term exposure to cytotoxic compounds. Cytotoxic drugs, crude tobacco products, benzo(a)pyrene, nicotine, and multiple other toxic compounds were shown to exhibit rapid PD-L1/PD-1 upregulation. A significant immunomodulatory effect of nicotine via acetylcholine receptors is well documented. However, nicotine activity rapidly subsides when the drug is withdrawn. We hypothesize that smoking cessation might mitigate the benefits of monoimmunotherapy for some patients. Further studies of the nicotinic acetylcholine receptor stimulus of immunocytes are needed and might lead to characterization and clinical implementation of new immunotherapy sensitizer products. BMJ Publishing Group 2021-08-19 /pmc/articles/PMC8378371/ /pubmed/34413168 http://dx.doi.org/10.1136/jitc-2021-003191 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Hypothesis
Zaleskis, Gintaras
Pasukoniene, Vita
Characiejus, Dainius
Urbonas, Vincas
Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy?
title Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy?
title_full Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy?
title_fullStr Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy?
title_full_unstemmed Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy?
title_short Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy?
title_sort do the benefits of being a smoker hint at the existence of pd-1/pd-l1 sensitizers for patients on single-agent immunotherapy?
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378371/
https://www.ncbi.nlm.nih.gov/pubmed/34413168
http://dx.doi.org/10.1136/jitc-2021-003191
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