Project description:RNAseq profiling of AZD3458 monotherapy and combination treatment with anti-PD-1 of whole tumors, isolated tumor macrophages (Mac) (CD45+CD11b+F4/80+), whole blood (PB) and tumor draining lymph nodes (TDLN) were assessed to elucidate further mechanisms leading to enhanced combination activity.
Project description:The effects of AKT/WEE1 inhibitors or ALDH inhibitor combined with PD-1 antibody on melanoma were examined. Mouse B16F10 melanoma cells were subcutaneously injected into C57/B6 mice. When tumors were well-vascularized, mice were treated with anti-PD-1, AKT I (AZD5363)+WEE1 I (MK1775), AZD5363+MK1775+anti-PD-1, ALDH I (KS100), KS100+ anti-PD-1 daily. Mice were sacrificed when tumors in the control group (DMSO treated) reached 2000 mm3 and tumors were removed. RNA was extracted from tumor samples and gene expression was analized using RNAseq analysis.
Project description:We performed single-cell RNA sequencing (scRNAseq) analysis on the mouse lung tissues from KP tumor-bearing mice treated with tumor cell intrinsic Asf1a KO, anti-PD-1 or combination treatment
Project description:We performed single-cell RNA sequencing (scRNAseq) analysis on the mouse lung tissues from small cell lung tumor-bearing mice treated with CDK7 inhibitor YKL, anti-PD-1 and combination treatment
Project description:We performed single-cell RNA sequencing (scRNAseq) analysis on the mouse lung tissues from small cell lung tumor-bearing mice treated with CDK7 inhibitor YKL, anti-PD-1 and combination treatment
Project description:We designed a study to investiagate chemo-immunotheraputic effect using a mouse model of colon cancer. To investigate the anti-tumor effect of the combination therapy, the in vivo antitumor activities of different mono- and combinational therapy were subsequently evaluated using a C57BL/6J mouse model bearing MC38 tumors. Subcutaneous injection of 1×106 of MC38 cells in the right flank of a mouse was performed 9 days before therapy. The Ru-PD-L1 was administrated by intraperitoneal injection, while the DPD or DOX was given by peritumoral injection. For combinational treatment, each mouse was treated with 14 µg DPD or DOX (0.56 mg/kg) 6 hours after administering 20 ug Ru-PD-L1 (0.80mg/kg). For monotherapy, each mouse was treated with Ru-PD-L1, DPD, or DOX alone. On the 20th day, the mice were sacrificed for tumor collection. The results highlighted that the combination of ACC and DOX prodrug synergistically enhanced immune response and higher antitumor activity compared to the ACC and DOX combination.
Project description:We use scRNA-seq to show the differences in tumor-infiltrating immune cells among IgG, anti-PD-1, anti-PSGL-1, and combination anti-PD-1 and anti-PSGL-1 treated mice. We show that anti-PSGL-1 treatment resulted in an increase in neutrophil and T cells, anti-PD-1 treatment resulted in an increase in macrophages, and the combination resulted in an increase in T cells and macrophages when compared to the tumors of IgG treated mice. Additionally, we show that Tregulatory cells are decreased in the tumors of anti-PSGL-1 and combination treated mice. Further, we find that anti-PSGL-1 treated CD8 T cells show upregulation of activation and survival genes, while combination treatment increased effector gene expression in CD8 T cells. Both anti-PSGL-1 treatment and combination treatment increase effector gene expression in CD4 T cells when compared to IgG. This scRNA-seq study shows the impact of IgG, anti-PD-1, anti-PSGL-1, and combination anti-PSGL-1 and anti-PD-1 antibody tteatment on tumor-infiltrating immune cells in B16-GP33 melnoma tumor bearing mice.
Project description:We determined the immune cell composition and their gene expression, by performing single-cell RNA sequencing (scRNA-seq), in anti-PD-L1-treated 2F8cis tumors, a hot and immunoresponsive ovarian murine tumor model, and anti-PD-L1-treated 2F8cis/CA-MSC tumors. We also evaluated the ability of hedgehog inhibitor (HHi) therapy to reverse CA-MSC effects. Adipose-derived mesenchymal stem cells (MSC) were cultured with 2F8cis, an ovarian mouse tumor cell line, to generate cancer-associated MSC (CA-MSC). 2F8cis tumor cell alone or 2F8cis/CA-MSCs co-cultured cells at ratio 1:1 were injected into C57BL/6J mice. Tumor infiltrating CD45+ cells were isolated from anti-PD-L1-treated 2F8cis (Group 1, n=3), anti-PD-L1-treated 2F8cis/CA-MSCs (Group 2, n=3), anti-PD-L1+ IPI-926-treated 2F8cis/CA-MSCs (Group 3, n=3) tumors. Samples were labeled with different TotalSeq oligo-conjugated antibodies and loaded into the Chromium instrument (10x Genomics). The resulting barcoded cDNAs were used to construct libraries. Single-cell cDNA libraries were then processed for RNA sequencing using an Illumina NextSeq-500 platform. Anti-PD-L1-treated 2F8cis/CA-MSC tumors showed a high number of Monocytes and macrophages over-expressing Ccr2 and Tgfbi when compared to anti-PD-L1 responsive 2F8cis tumors. Our results also indicated that IPI-926 restored response to anti-PD-L1 therapy decresing the expression of Ccr2 and Tgfbi both in monocytes and macrophages. Our study represents the first detailed analysis generated by RNA-seq technology of 2F8cis/CA-MSC+ enriched tumor transcriptomes, treated with anti-PDL1 alone or in combination with HHi, and compared with anti-PDL1-treated tumors. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles.
Project description:Analyzing mouse tumor models in vivo, human T cells ex vivo and human lung cancer samples, we provide direct evidence that NR2F6 acts as novel immune checkpoint. Genetic ablation of Nr2f6, particularly in combination with blockade of the established PD-L1 cancer immune checkpoint, efficiently delayed tumor progression and improved survival in experimental mouse models. The target genes deregulated in intratumoral T lymphocytes upon genetic ablation of Nr2f6 alone or together with PD-L1 blockade, revealed multiple advantageous transcriptional alterations for effective tumor rejection. In keeping with the above observation, acute Nr2f6 silencing in both mouse and human T cells induced hyper-responsiveness that established a non-redundant T cell-inhibitory function of NR2F6. Analyzing mouse tumor models in vivo, human T cells ex vivo and human lung cancer samples,