Anti PD-1/PD-L1

PD-1 (Programmed Cell Death Protein 1) is a receptor expressed on the surface of T cells that plays a critical role in regulating the immune response. Tumor cells express PD-L1 as an "adaptive immune strategy" to evade anti-tumor immune responses. The interaction between PD-L1 and PD-1 inhibits the anti-tumor response by blocking T-cell activation. 


Inhibitors of the PD-1/PD-L1 interaction (block PD-1/PD-L1 binding)
          Shikonin {ref}
Kaempferol
          Quercetin 
Apigenin
Fisetin
Licorice (weak)
Ellagic acidUnripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction {study}


Downregulation of PD-L1 (PD-L1 downregulation could reverse immunosuppression)
Suppressing HIF-1α and STAT3 can lead to the downregulation of PD-L1 expression. Silibinin and baicalein (via STAT3) 
Orlistat: Fatty acid synthase inhibitor orlistat impairs cell growth and down-regulates PD-L1 expression of a human T-cell leukemia line  {study}
DHA (Docosahexaenoic acid){ref}
Berberine
Shiitake (lentinan)
Chlorogenic acid
Cardamom {ref}


Copper supplementation enhances PD-L1 expression, driving cancer immune evasion, while copper chelation promotes ubiquitin-mediated degradation of PD-L1 and increases the number of tumor-infiltrating CD8+T and natural-killer cells.{ref}

PD-1 blockade: opening the door to attack

Looking for the Optimal PD-1/PD-L1 Inhibitor in Cancer Treatment


Synergies

Ivermectin induces immunogenic cancer cell death (ICD) and robust T-cell infiltration {ref}
Artemisinin promotes the proliferation of CD4 + T and CD8 + T cells
Butyrate can exert anti-cancer effects by stimulating CD8+ T cells and increasing their effector function {ref}
AHCC
Niclosamide

https://pubmed.ncbi.nlm.nih.gov/31511071/







Mechanism of action of nivolumab. PD-1 (expressed by activated T cells) is blocked by PD-L1 (expressed by tumour cells), thus inhibiting the immune response (A). Nivolumab binds to PD-1 and blocks its interaction with the PD-L1 ligand, which restores the antitumour immunity (B).





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