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 acid: Unripe 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}

Methionine metabolism also influences immune checkpoints like PD-L1. SAMe-dependent methylation regulates PD-L1 mRNA stability, enhancing immune evasion. Restricting methionine (and by extension, B12/folate) reduces PD-L1 expression, but excess levels could counteract this.

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

Lin, Jichun & Fang, Wenshuo & Xiang, Zhuo & Wang, Qingqing & Cheng, Huapeng & Chen, Shimin & Fang, Jing & Liu, Jia & Wang, Qiang & Lu, Zhimin & Ma, Leina. (2023). Glycolytic enzyme HK2 promotes PD-L1 expression and breast cancer cell immune evasion. Frontiers in Immunology. 14. 10.3389/fimmu.2023.1189953.

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