Fig 1: Anti-PD1/chidamide shows an immune response with epigenetic regulation. a, Western blot of Ifn-?, Cxcl9, Cxcr3, Acetylated histone H3, histone H3, Pd-l1, and ß-actin in anti-PD1/chidamide and each monotherapy. b, Western blot of Ifn-?, Cxcl9, Cxcr3, Acetylated histone H3, histone H3, Pd-l1, and ß-actin in anti-PD1/romidepsin and each monotherapy. c, ELISA of tumour lysis in anti-PD1/chidamide. d, ELISA of tumour lysis in anti-IFN-? neutralization. e, Heatmap of ChIP-seq in high-dose, low-dose anti-PD1/chidamide, high-dose anti-PD1/romidepsin. f, Acetylated level of immune responses factor Ifn-?, Gzmb, Gzmk, and Cxcr3 (left to right). g, ChIP-qPCR validation of Ifn-? and Cxcr3 in different groups of anti-PD1/chidamide and anti-PD1/romidepsin. h, immunohistochemistry staining of Cd8, Cxcl9, Ifn-?, and Pd-l1 in anti-PD1/chidamide. i, immunohistochemistry staining of Cd8, Cxcl9, Ifn-?, and Pd-l1 in anti-PD1/romidepsin. j, immunohistochemistry staining of Cd8, Cxcl9, Ifn-?, and Pd-l1 in anti-PD1/romidepsin or anti-PD1/chidamide ± anti- Ifn-? (*P<0.05,**P<0.001, ***P<0.0001, Mann–Whitney U-test and one-way ANOVA).
Fig 2: Anti-PD1/chidamide shows promising efficiency in clinical and its mechanism scenario. a, Case 1 is a female patient with NK-T cell lymphoma who received more than 2-year treatment of anti-PD1 and chidamide after refractory from first-line chemotherapy. b, Case 2 is a female patient with NK-T cell lymphoma who received anti-PD1 and chidamide as maintenance treatment after first-line chemotherapy finished. c, anti-PD1/Chidamide combination induces chemokine expression in multiple cell types resulting in enhanced immune cell recruitment, trafficking and infiltration. Chemokine ligands and receptors binding include Cxcr3-Cxcl9/10/11 in CD8 T-tumour cells or NK-tumour cells and Ccr5-Ccl4/Ccl5/Ccl20 in dendritic-tumour cells. Besides, the combination enhances IFN-? expression and acetylated level in multiple cell types resulting in enhanced antigen presentation, T cell activation, immune cell infiltration, and tumour cell killing. Cd274 is also upregulated by IFN-? as a feedback loop and tumour cells become more responsive to anti-PD1 treatment. By contrast, there was no additive anti-tumour effect when romidepsin combined with anti-PD1, including no changes in chemokines and IFN-? responses.
Supplier Page from CUSABIO Technology LLC for Mouse C-X-C motif chemokine 9(CXCL9) ELISA Kit