Title Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy? /
Authors Zaleskis, Gintaras ; Pašukonienė, Vita ; Characiejus, Dainius ; Urbonas, Vincas
DOI 10.1136/jitc-2021-003191
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Is Part of Journal for immunotherapy of cancer.. London : BMJ. 2021, vol. 9, iss. 8, p. 1-4.. ISSN 2051-1426. eISSN 2051-1426
Keywords [eng] cellular ; combination ; drug evaluation ; drug therapy ; immunity ; immunomodulation ; immunotherapy ; preclinical
Abstract [eng] 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 However, nicotine activity rapidly subsides when the drug is withdrawn.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.
Published London : BMJ
Type Journal article
Language English
Publication date 2021
CC license CC license description