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Activation of tumor-specific CD8+ T cells prior to radiopharmaceutical therapy improves anti-tumor response

ABSTRACT: Previously, we found that the presence and activation of tumor-specific CD8+ T cells prior to radiopharmaceutical therapy (RPT), 90Y-NM600, enhanced anti-tumor responses. Here, we aimed to evaluate changes in the tumor immune microenvironment after E.G7-OVA tumor-bearing mice received adoptive transfer of naïve OT-I CD8+ T cells, followed by a DNA vaccine, and 90Y-NM600. Tumors were collected 7 and 14 days following 90Y-NM600, isolated total RNA, and performed gene expression analysis using the nCounter Mouse Immune Exhaustion Panel on the nCounter MAX system.

ORGANISM(S): Mus musculus

PROVIDER: GSE330657 | GEO | 2026/06/19

REPOSITORIES: GEO

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Gene expression profiles of OT-1 T cells co-cultured with MHC-I Negative Tumors and Antigen Loaded Macrophages

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Radiopharmaceuticals enhance CAR T-cells against radio-sensitive and radio-resistant neuroblastoma by tumor sensitization and TME remodeling [scRNA-Seq]

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Expression data from OT-I CD8 T cells activated with DC in the presence or absence of CpG-Induced Inflammation

Project description:Inflammatory cytokines promote the accumulation of activated CD8 T cells. Here, we transfer 600 OT-I CD8 T cells iv into naÃ¯ve C57BL/6 hosts. One day later, 500,000 LPS-matured and OVA257 peptide-coated DC were injected iv into OT-I CD8 T cell seeded hosts with (DC+CpG) or without (DC). Other seeded mice were infected with 2x10^4 virulent Listeria monocytogenes (vLM-OVA) iv. OT-I CD8 T cells were harvested from the spleen, flow sort purified, then RNA was extracted using RNeasy (Qiagen) kit. Naive OT-I CD8 T cells (Naive) were purified from the spleens of OT-I transgenic mice. Each group had three independent biological replicates.Transcriptomes were compared using DAVID analysis (with genes scoring FDR<0.01) and GSEA analysis. 3 biological replicates per group. Groups included NaÃ¯ve OT-I CD8 T cells, DC+CpG OT-I CD8 T cells, DC OT-I CD8 T cells, and vLM-OVA OT-I CD8 T cells. Most comparisons used NaÃ¯ve OT-I CD8 T cells as a baseline comparison

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Activation of tumor-specific CD8+ T cells prior to radiopharmaceutical therapy improves anti-tumor response

Project description:Activation of tumor-specific CD8+ T cells prior to radiopharmaceutical therapy improves anti-tumor response

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Adoptive transfer of membrane-restricted IL-12-TCR T cells promotes antigen-spreading and elimination of antigen-negative tumor variants

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Whole-genome microarray analysis of primary, secondary, tertiary and quaternary memory CD8 T cells

Project description:The transcriptome of naive OT-I T cells was compared to memory CD8 T cells after 1, 2, 3, or 4 infection with ovalbumin expressing Listeria monocytogenes (LM-OVA). Naive Thy1.1 OT-I T cells were adoptively transferred into Thy1.2 naive hosts prior to infection with LM-OVA. The resulting memory CD8 T cell population was again adoptively transferred into naive hosts and the recipient mice were again infected with LM-OVA. The adoptive transfer was repeated up to four times to generate memory CD8 T cells with up to four consecutive antigen stimulations. Three individual mice were analyzed for each group. For quaternary memory CD8 T cells, spleens from two to three mice were pooled for each sample. Naive OT-I T cells served as control samples. http://dx.doi.org/10.1016/j.immuni.2010.06.014

2010-07-09 | E-GEOD-21360 | biostudies-arrayexpress

TCR beta sequencing of blood and tumor samples from EG7.OVA bearing wildtype mice with OT-1 T cell transfer

Project description:We report the application of TCRβ sequencing to understand T cell repertoire of matched blood and tumor samples pre and post treatment in EG7.OVA tumor bearing mice with OT-1 cell transfer. TCRβ sequencing demonstrated that OT-1 (CASSRANYEQYF) was the most abundant T-cell clone in both blood and tumors of mRBC‑OVA-4-1BBL-IL-12 treated mice. To investigate the effects of mRBC‑OVA-4-1BBL-IL-12 on immune memory, the T cell repertoire was also analyzed before and after EG7.OVA and EL4 tumor rechallenge in cured and treatment-naive mice. TCRβ sequencing on T cells in peripheral blood showed that OT-1 clones increased in frequency after EG7.OVA challenge in previously cured mice. OT-1 frequency did not increase in treatment-naïve mice after tumor challenge, indicating that the tumor alone is insufficient to drive OT-1 cell expansion. We also evaluated the frequencies of unique TCRβ sequences in T cell clones that significantly expanded post EL4 challenge (EL4 responsive TCR). Increased frequency of EL4-responsive TCRs upon each tumor challenge (EG7.OVA and EL4) was associated with complete responders (mice that rejected EL4 challenge), suggesting that T-cell-mediated protection against parental tumor antigens was generated prior to EL4 challenge. Partial responders (delayed tumor growth compared with naïve mice) had increases in EL4-responsive TCR frequencies after EL4 challenge but not during the EG7.OVA rechallenge, whereas the non-responder (tumor growth similar to naïve mice) had minimal increases in TCR frequencies upon EL4 challenge. Overall, the ability to control EL4 tumors correlated with the expansion of EL4-responsive TCR clones.

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Bulk RNAseq of OT-1 T cells in OVA-pregnant and OVA-grafted mice

Project description:Purpose: The molecular circuits which govern CD8 T cell fate after alloimmunization by transplantation or pregnancy are unknown. The goals of this study are to perform whole transcriptome profiling (RNA-seq) of antigen-experienced CD8 T cells in parous and grafted mice to determine whether these cells become memory or exhausted T cells. Methods: mRNA profiles of OT-1 T cells recovered fom naive,OVA-skin grafted and OVA-parous mice were generated by bulk RNA-sequencing. OT-1 cells were FACS sorted from 10 individual mice per each of the three groups and then pooled together into three replicate samples per group. The sequence reads that passed quality filters were analyzed after aligning (STAR) with EdgeR. Results: Comparison of OT-1 T cells from OVA-grafted and OVA-parous mice revealed 400 differentially expressed genes. Conclusions: Skin grafting promotes the differentiation of canonical memory CD8 T cells whereas pregnancy promotes the differentiation of exhausted CD8 T cells with diminished recall capacity.

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