HSP90α induces immunosuppressive myeloid cells in melanoma via TLR4 signaling.
Ihor ArkhypovFeyza Gül Özbay KurtRebekka BitschDaniel NovakVera PetrovaSamantha LasserThomas HielscherChristopher GrothAlisa LepperXiaoying HuWei LiJochen UtikalPeter AltevogtViktor UmanskyPublished in: Journal for immunotherapy of cancer (2022)
Our findings demonstrated that soluble rHSP90α increased the resistance of normal human monocytes to apoptosis and converted them into immunosuppressive MDSC via TLR4 signaling that stimulated PD-L1 and IDO-1 expression. Furthermore, patients with melanoma with high concentrations of HSP90α displayed increased PD-L1 expression on M-MDSC and reduced PFS after ICI therapy, suggesting HSP90α as a promising therapeutic target for overcoming immunosuppression in melanoma.
Keyphrases
- heat shock protein
- cell cycle arrest
- heat shock
- heat stress
- toll like receptor
- induced apoptosis
- inflammatory response
- skin cancer
- immune response
- dendritic cells
- endoplasmic reticulum stress
- endothelial cells
- poor prognosis
- oxidative stress
- cell death
- basal cell carcinoma
- bone marrow
- acute myeloid leukemia
- pi k akt
- stem cells
- induced pluripotent stem cells
- binding protein
- pluripotent stem cells
- cell proliferation