Cancer name Lymphoma
Cancer Type DLBC
Immunotherapy type Immunostimulant OR Targeting Therapy
Treatment SB415286
Drugstatus NA
Drugbank ID NA
Checkpoints NA
Signature Type Protein
Signature PD-1
Official Symbol PDCD1
Mode of action PROT_D_DOWN
Description for ‘mode of action’：the ‘mode of action’ for signature is composed of three parts: A_B_C. A describes the level at which the corresponding signature changes, it may contain the following values: TRAN(translation), PROT(protein), CE(cell), METH(methylation), AC(acetylation), PHOS(phosphorylation), MU(mutation), SNP(single nucleotide polymorphism), GLYC(glycosylation) and PATH(pathway). B describes the corresponding signature in which cancer immunotherapy condition group has changed, it may contain the following values: R (immunotherapy response group), NR(immunotherapy non-response group), D (Immunotherapy group), ND (No immunotherapy group). C describes the change detail (specific direction) of the corresponding signature, it may contain the following values: UP (High gene/protein expression or increased cellular abundance or enhanced epigenetic modification), DN (Low gene/protein expression or reduced cellular abundance or attenuated epigenetic modifications), LOSS (deletion mutation), GAIN (gain mutation)，Other. For example, the search/browse detail result for CD274 was “PROT_R_UP”, it can be interpreted that the protein level of CD274 was upregulated in immunotherapy response individuals.
Experimental mouse model
Description Furthermore, the conditional genetic deletion of GSK-3α/β reduced PD-1 expression on CD8+ T cells and limited B16 pulmonary metastasis to the same degree as PD-1 gene deficiency. In each model, GSK-3i inhibited PD-1 expression on tumor-infiltrating lymphocytes, while increasing Tbx21 (T-bet) transcription, and the expression of CD107a+ (LAMP1) and granzyme B (GZMB) on CD8+ T cells. Finally, the adoptive transfer of T cells treated ex vivo with a GSK-3 inhibitor delayed the onset of EL4 lymphoma growth to a similar extent as anti-PD-1 pretreatment. Overall, our findings show how GSK-3 inhibitors that downregulate PD-1 expression can enhance CD8+ T-cell function in cancer therapy to a similar degree as PD-1-blocking antibodies.
PMID 29055015
Title Small-Molecule Inhibition of PD-1 Transcription Is an Effective Alternative to Antibody Blockade in Cancer Therapy