RT Journal Article
SR Electronic
T1 Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy?
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e003191
DO 10.1136/jitc-2021-003191
VO 9
IS 8
A1 Gintaras Zaleskis
A1 Vita Pasukoniene
A1 Dainius Characiejus
A1 Vincas Urbonas
YR 2021
UL http://jitc.bmj.com/content/9/8/e003191.abstract
AB 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 However, nicotine activity rapidly subsides when the drug is withdrawn.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.