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Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules

N. Abramenko, F. Vellieux, K. Veselá, Z. Kejík, J. Hajduch, M. Masařík, P. Babula, D. Hoskovec, K. Pacák, P. Martásek, K. Smetana, M. Jakubek

. 2024 ; 14 (1) : 3043. [pub] 20240206

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24007195

Grantová podpora
LX22NPO5102 and LX22NPO5107 European- Union
LX22NPO5102 and LX22NPO5107 European- Union
LX22NPO5102 and LX22NPO5107 European- Union
SVV260637; SVV260521; UNCE 204064; Progres LF1 Q38 and Q27, Cooperatio ONCO Charles University
. LM2023053 Ministry of Education, Youth, and Sports
TN02000109 Technology Agency of the Czech Republic
NU22-D-136 and NU21-08-00407 the Ministry of Health

Immune checkpoints regulate the immune system response. Recent studies suggest that flavonoids, known as phytoestrogens, may inhibit the PD-1/PD-L1 axis. We explored the potential of estrogens and 17 Selective Estrogen Receptor Modulators (SERMs) as inhibiting ligands for immune checkpoint proteins (CTLA-4, PD-L1, PD-1, and CD80). Our docking studies revealed strong binding energy values for quinestrol, quercetin, and bazedoxifene, indicating their potential to inhibit PD-1 and CTLA-4. Quercetin and bazedoxifene, known to modulate EGFR and IL-6R alongside estrogen receptors, can influence the immune checkpoint functionality. We discuss the impact of SERMs on PD-1 and CTLA-4, suggesting that these SERMs could have therapeutic effects through immune checkpoint inhibition. This study highlights the potential of SERMs as inhibitory ligands for immune checkpoint proteins, emphasizing the importance of considering PD-1 and CTLA-4 inhibition when evaluating SERMs as therapeutic agents. Our findings open new avenues for cancer immunotherapy by exploring the interaction between various SERMs and immune checkpoint pathways.

Citace poskytuje Crossref.org

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