| Cancer name | Skin Cutaneous Melanoma |
| Cancer Type | SKCM |
| Immunotherapy type | Immune Checkpoint Therapy;Immunostimulant OR Targeting Therapy |
| Treatment | anti-AB |
| Drugstatus | NA |
| Drugbank ID | NA |
| Checkpoints | PD-1/PD-L1/CTLA-4 |
| Signature Type | Cell |
| Signature | CD3- CD49b+ NK Cell |
| Official Symbol | NA |
| Mode of action | CE_D_UP |
| 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 | We observed that combined treatment of B16F10-tumor bearing mice with selinexor and anti-PD-L1 antibody significantly increased the frequency of NK cells (CD3- CD49b+) in the spleen (p=0.0063; Fig. 3.b.). |
| PMID | 28148715 |
| Title | The impact of XPO1 inhibition on the expression of CD274 was also evaluated in human (A375, CHL-1) and murine (B16F10) melanoma cell lines. These three cell lines were treated with 1 μM selinexor for 24 hours and CD274 transcript levels quantified by qPCR. Selinexor treatment induced a significant increase in CD274 expression in human melanoma cell lines (A375, CHL-1) (p=0.0015 and p<0.0001, respectively Fig. 1b). However, 24 hours of selinexor treatment resulted in a modest though significant decrease in Cd274 mRNA expression in the murine B16F10 cell line (p=0.0006, Fig. 1b). Selinexor also significantly upregulated CD274transcript in other human cancer cell lines, including breast (MDA-MB-468), sarcoma (ASPS-KY), and prostate (PC3) (MDA-MB-231 p<0.0001, ASPS-KY and PC3 p<0.05, Fig. 1c), indicating this effect was not exclusive to melanoma. At the protein level, and consistent with prior reports (15), expression of PD-L1 on the surface of the human and murine melanoma cell lines was evident at baseline (Fig. 1d.). While CD274 mRNA levels were altered following selinexor treatment, the high basal levels of surface protein expression of PD-L1 were not decreased in any of these cell lines by in vitro selinexor treatment at up to 1 μM (data not shown). |