| Cancer name | Lung Adenocarcinoma |
| Cancer Type | LUAD |
| Immunotherapy type | Immune Checkpoint Therapy |
| Treatment | anti-PD-1 antibod |
| Drugstatus | NA |
| Drugbank ID | NA |
| Checkpoints | PD-1 |
| Signature Type | Protein |
| Signature | CXCL9 |
| Official Symbol | CXCL9 |
| Mode of action | TRAN_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 | 1. Importantly, romidepsin significantly enhanced the response to PD-1 blockade immunotherapy in multiple lung tumor models, including nearly complete rejection in two models. Combined romidepsin and PD-1 blockade also significantly enhanced activation of tumor-infiltrating T cells. 2.Microarray studies showed that many of the romidepsin induced genes were known targets of IFNγ (e.g. T cell chemokines, MHC and FAS) . Interestingly, expression of the key IFNγ-induced transcription factor STAT1 was also increased by romidepsin , potentially linking effects of this HDACi to IFNγ signaling. 3. Previous studies have demonstrated that anti-PD-1 enhances T cell chemokine expression and T cell infiltration, and that this effect is mediated by IFNγ production. Based upon the ability of IFNγ to synergistically promote chemokine expression with romidepsin in vitro, we postulated that IFNγ was also a central regulator of the anti-tumor response seen with romidepsin and anti-PD-1 in vivo. Consistent with this interpretation, combination therapy in mice bearing LKR tumors increased tumor expression of Cxcl10 and Cxcl9 by 50-fold and 15-fold, respectively. 4.We next determined whether IFNγ was functionally required to promote chemokine expression and mediate the anti-tumor effects of combination therapy.. Finally, we found that IFNγ neutralization ablated the effects of combination therapy, with tumor growth comparable to untreated controls. |
| PMID | 26964571 |
| Title | HDAC Inhibitors Enhance T-Cell Chemokine Expression and Augment Response to PD-1 Immunotherapy in Lung Adenocarcinoma |