A fatty acid-rich fraction of an endolichenic fungus Phoma sp. suppresses immune checkpoint markers via AhR/ARNT and ESR1

• Published in: Heliyon Vol. 9; no. 9; p. e19185
• Main Authors: Varlı, Mücahit, Ngo, Men Thi, Kim, Seong-Min, Taş, İsa, Zhou, Rui, Gamage, Chathurika D.B., Pulat, Sultan, Park, So-Yeon, Sesal, Nüzhet Cenk, Hur, Jae-Seoun, Kang, Kyo Bin, Kim, Hangun
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.09.2023; Elsevier
• Subjects: Aryl hydrocarbon receptor; Endolichenic fungi; Estrogen receptor; Immune checkpoint markers; Natural product; Programmed death ligand 1; Estrogen receptor; Programmed death ligand 1; DMSO; Sp2 transcription factor; FOXG1; POU class 2 homeobox associating factor 1; nuclear factor kappa B; ITS; TLC; Immune checkpoint markers; GATA3; VTCN1; BaP; MFI; HVEM; HNF4A; potato dextrose agar; EGR1; HSP90; Sp1 transcription factor; CREBBP; Natural product; ARNT; AhR; ICOSL; programmed death-ligand 1; signal transducer and activator of transcription 3; Fluorescence Intensity; ESR1; GC-MS; Aryl hydrocarbon receptor; LC-MS; nuclear factor of activated T cells 3; nuclear factor of activated T cells 2; VISTA; myogenic factor 5; Endolichenic fungi; 4-1BBL; nuclear factor of activated T cells 4; ATF3; ELF; ATF4
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2023.e19185

Lung cancer has the highest mortality rates worldwide. The disease is caused by environmental pollutants, smoking, and many other factors. Recent treatments include immunotherapeutics, which have shown some success; however, the search for new therapeutics is ongoing. Endolichenic fungi produce a whale of a lot of secondary metabolites, the therapeutic effects of which are being evaluated. Here, we used a crude extract and subfractions of the endolichenic fungus, Phoma sp. (EL006848), isolated from the Pseudevernia furfuracea. It was identified the fatty acid components, palmitic acid, stearic acid, and oleic acid, exist in subfractions E1 and E2. In addition, EL006848 and its fatty acids fractions suppressed benzo[a]pyrene (an AhR ligand)- induced expression of PD-L1 to inhibit the activity of multiple immune checkpoints. E2 subfraction, which had a higher fatty acid content than E1, downregulated expression of AhR/ARNT and several human transcription factors related to ESR1. Moreover, E2 showed a strong inhibitory effect on STAT3 expression and mild effect on NF-kB activity. These results suggest that fatty acids extracted from an endolichenic fungus can exert strong immunotherapeutic effects.