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Post-ICB treatment PDAC infiltrating T cells TCR profile

ABSTRACT: For the subcutaneous model, 5x105 KPC-Luc cells were injected subcutaneously near the right flank of female C57BL/6 mice. 6-7 days after tumor implantation mice were randomized into 4 treatment groups and treatedwith VIP-R antagonist and/or anti-PD-1. While scram+IgG control mice received scrambled peptide and isotype IgG, the VIP-R antagonist, anti-PD-1 and VIP-R antagonist and anti-PD-1 groups received VIP-R antagonist and IgG; scrambled peptide and anti-PD-1; and VIP-R antagonist and anti-PD-1, respectively. The treatment regimen involved administering 10μg of scrambled or VIP-R antagonist: ANT008, subcutaneously every day and 200μg of IgG or anti-PD-1 intraperitoneally once every three days, for a total of 10 days.

ORGANISM(S): Mus musculus

PROVIDER: GSE213482 | GEO | 2022/09/19

REPOSITORIES: GEO

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Post-ICB treatment PDAC infiltrating T cells gene expression

Project description:For the subcutaneous model, 5x105 KPC-Luc cells were injected subcutaneously near the right flank of female C57BL/6 mice. For the MT5 or Panc02 models, 5x105 were injected subcutaneously near the right flank of female C57BL/6 mice. For the orthotopic KPC-Luc model, mice were anesthetized, and the KPC-Luc cells were suspended in Matrigel and injected in the tail of the pancreas following laparotomy. 6-7 days after tumor implantation mice were randomized into 4 treatment groups and treatedwith VIP-R antagonist and/or anti-PD-1. While scram+IgG control mice received scrambled peptide and isotype IgG, the VIP-R antagonist, anti-PD-1 and VIP-R antagonist and anti-PD-1 groups received VIP-R antagonist and IgG; scrambled peptide and anti-PD-1; and VIP-R antagonist and anti-PD-1, respectively. The treatment regimen involved administering 10μg of scrambled or VIP-R antagonist: ANT008 or ANT308, subcutaneously every day and 200μg of IgG or anti-PD-1 intraperitoneally once every three days, for a total of 10 days.

2022-09-21 | GSE213778 | GEO

Phase II randomised clinical trial of personalized peptide vaccination in combination with Dai-kenchu-to for colorectal cancer patients resistant to standard therapies.

Project description:Interventions: arm1: The right peptides (up to 4 peptides) for vaccination to individual patients will be selected in consideration of the pre-existing host immunity assessed by the titers of anti-peptide IgG before vaccination, and subcutaneously injected with incomplete Freund’s adjuvant every week (3.0 mg/each peptide; 6 times/cycle). Dai-kenchu-to(5 g/time, 3 times/day) will be orally administered from the date of the first vaccination to the date of the sixth vaccination. If the patients want to continue the vaccination after completion of the first cycle of 6 vaccinations, the peptide vaccination will be allowed to continue (every 2-4 weeks). arm2: The right peptides (up to 4 peptides) for vaccination to individual patients will be selected in consideration of the pre-existing host immunity assessed by the titers of anti-peptide IgG before vaccination, and subcutaneously injected with incomplete Freund’s adjuvant every week (3.0 mg/each peptide; 6 times/cycle). If the patients want to continue the vaccination after completion of the first cycle of 6 vaccinations, the peptide vaccination will be allowed to continue (every 2-4 weeks). Primary outcome(s): Comparison of immune-enhancing effects (changes in anti-peptide IgG titers in plasma)between two groups. Study Design: Parallel Randomized

| 2623536 | ecrin-mdr-crc

Phase I Clinical trial of personalized peptide vaccine in combination with humanized anti-IL6 receptor monoclonal antibody for refractory colorectal cancer patients

Project description:Interventions: Anti-IL6 receptor antibody [Actemra (tocilizumab), Chugai Pharmaceutical Co; 0.5mg/kg (n=6), 2mg/kg (n=6), or 8mg/kg (n=6)] is intravenously administrated. After three days, a maximum of 4 peptides (3 mg/each peptide), which are selected based on the results of HLA typing and peptide-specific IgG titers, are subcutaneously administrated with incomplete Freund’s adjuvant (Montanide ISA51, Seppic)once a week for consecutive 6 weeks. During the treatment, safety is evaluated.The dose of anti-IL6 receptor antibody is escalated, if the safty is confirmed in 6 independent patients at the same dose. Primary outcome(s): Safety (adverse events) of personalized peptide vaccine in combination with anti-IL6 receptor antibody. Study Design: Single arm Non-randomized

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Effects of anti-PD-L1 on the testis transcriptomes of C57BL/6 mice

Project description:To explore the mechanisms of the decreased testosterone after anti-PD-L1 treatment in mice, we performed RNAseq transcriptome analysis of the testes of male mice 7 days later post-treatment with anti-PD-L1 or control IgG. After quantified by TBS380, paired-end RNA-seq sequencing library was sequenced with the Illumina HiSeq xten. Our results show that pathways involved in both lipid transportation and inflammation were obviously affected by anti-PD-L1 treatment.

2021-10-06 | GSE171229 | GEO

The effect of depletion of VPAC2 on gene expression in Panc02 Pancreatic Ductal Adenocarcinoma cell line

Project description:Identifying mechanisms underlying tumor growth and immune resistance is needed to treat pancreatic ductal adenocarcinoma (PDAC) effectively. The complexity of the tumor microenvironment (TME) suggests that the crosstalk between cells in the TME could drive drug resistance and relapse in PDAC. We have previously determined that vasoactive intestinal peptide (VIP) is overexpressed in PDAC and that VIP receptors expressed on T cells are a targetable pathway that sensitizes PDAC to anti-PD1 therapy. In this study, we show that pancreatic cancer cells engage in autocrine signaling of VIP through VIP-receptor 2 (VPAC2), and that high co-expression of VIP with VPAC2 leads to reduced relapse-free survival in PDAC patients. Mechanistically, we identified piwi-like RNA-mediated gene silencing2 (Piwil2) as a tumor-cell intrinsic protein downstream of VPAC2 that regulates cancer cell growth. In addition, we discovered TGFβ-1 as a potential tumor-extrinsic inhibitor of T cell function induced by VPAC2 signaling. In vivo, knock out and knockdown of VPAC2 on PDAC cells led to reduced tumor growth rate and increased sensitivity to anti-PD-1 therapy in various mouse models of PDAC that were T- cell dependent. Overall, these findings emphasize the implications of VIP/VPAC2 signaling in the PDAC tumor microenvironment and further support the rationale for developing VPAC2-specific antagonists.

2023-12-04 | GSE248409 | GEO

scRNA-seq comparison of B16-GP33 tumor-infiltrating immune cells from IgG, anti-PD-1, anti-PSGL-1, or combination anti-PD-1 and anti-PSGL-1 treated mice

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.

2022-02-07 | GSE196112 | GEO

GATM PPMO knockdown affects host response to H1N1 influenza infection in mouse lungs

Project description:The GATM gene shows strong transcriptional regulation during influenza infection and increased GATM transcription correlates with peak viral titers in the lung. In order to investigate an in vivo role for GATM during influenza infection, we created a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) to disrupt GATM translation. In our study, mice received a GATM-specific PPMO or scrambled PPMO once per day for two days, and then were subsequently infected with an H1N1 (A/California/04/2009) strain of IAV or PBS as a mock infection control. Mouse lungs were harvested three days post-infection and analyzed via RNA sequencing.

2021-08-02 | GSE181246 | GEO

Anti-PD-1/anti-CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8+ T cell trafficking

Project description:Intracranial B16 melanoma tumors isolated from C57Bl6 mice were analyzed by mRNAseq. Four experimental groups were analyzed: (1) Mice with intracranial tumors receiving IgG; (2) Mice with intracranial tumors receiving anti-PD-1 plus anti-CTLA-4 therapy; (3) Mice with intracranial plus extracranial tumors receiving IgG; (4) Mice with intracranial plus extracranial tumors receiving anti-PD-1 plus anti-CTLA-4 therapy. Taggart et al., PNAS 2018;

2018-02-01 | GSE109485 | GEO

Impaired innate and adaptive immune responses to BNT162b2 SARSCoV-2 vaccination in systemic lupus erythematosus [CTD]

Project description:We measued IgG autoantibodies associated with Connective Tissue Diseases (CTDs) and Anti-Cytokine Antibodies (ACA) in SLE and healthy controls who received the BNT162b2 vaccine.

2024-03-02 | GSE260478 | GEO

Impaired innate and adaptive immune responses to BNT162b2 SARSCoV-2 vaccination in systemic lupus erythematosus [ACA]

2024-03-02 | GSE260475 | GEO

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