Characterization of tumor-infiltrating T cells by TCR-β repertoire analyses
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE126278 | GEO | 2019/02/13
REPOSITORIES: GEO
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Project description:Local administration of IFN-α-producing proliferating myeloid cells (IFN-α-iPSC-pMCs) inhibited the tumor growth not only at the treatment site (right) but also at the distant site (left). We identified genes with log fold expression change ≥ 1 or ≤ −1 in untreated versus IFN-α-iPSC-pMC-treated tumors and iPSC-pMC-treated versus IFN-α-iPSC-pMC-treated tumors for treatment or distant site, respectively. Of the overlapping genes differentially expressed in IFN-α-iPSC-pMC-treated mice, 301/671 distant site and 460/928 treated site genes were ISGs, of which 95.3% and 94.7%, respectively, were type I IFN-related. By gene ontology, the up-regulated ISG signatures were enriched for “T cell-mediated immune responses”, “cytolysis”, and “migration of immune cells” associated genes. Collectively, Local administration of IFN-α-iPSC-pMCs alters the tumor microenvironment and propagates molecular signature associated with type I IFN.
2019-02-13 | GSE126279 | GEO
Project description:We previously established a method to generate myeloid lineage cells with proliferation capacity from induced pluripotent stem cells (iPSCs) (Zhang R. Cancer Immunol Res. 3: 668, 2015). In this study, we generated the IFN-α-producing cells by genetic engineering of mouse iPSC-derived myeloid cells (iPSC-pMCs). Gene expression profiling of IFN-α-producing iPSC-pMCs (IFN-α-iPSC-pMCs) revealed a distinct interferon-stimulated gene (ISG) signature: of 613 differentially expressed genes (versus iPSC-pMC), 345 genes were ISGs of which > 70 % were type I IFN-related. Gene ontology analysis showed that the up-regulated gene signature was enriched for transcripts associate with immune responses, cellular responses to type I IFN, and defense responses to virus.
2019-02-13 | GSE126277 | GEO
Project description:In our study, we have characterized the non-expanded and expanded tumor-infiltrating lymphocytes (TILs) from treatment-naive renal cell carcinoma (RCC) patients (n=3), as well as the minimally cultured pre-REP TILs and rapidly expanded REP TILs with a clinical-grade TIL expansion protocol. We observed that the REP TILs encompassed an abundance of CD4positive T-cells, together with increased LAG-3 and low PD-1 expression in the CD4positive and CD8positive T-cells. In addition, we observed that the TIL expansion protocol expanded small CD4positive T-cell clonotypes in the tumor microenvironment (TME), and that the large, exhausted tumor T-cell clonotypes do not expand. We further identified RCC-associated TCR motifs that were validated in multiple TCRalpha-beta-seq and scRNAand TCRalpha-beta-seq datasets, as well as quantified the RCC-associated TCRs from the REP protocol. Overall, the T-cells carrying the RCC-associated TCRs remained high in the tumors and corresponding pre-REP TILs, but the frequency was reduced in the REP TILs. Furthermore, the overall anti-viral TCRs remained low throughout the REP protocol. Our results provide an in-depth understanding of the origin, immunophenotype, and specificity of the TCRs in RCC TILs.
2023-12-29 | E-MTAB-12910 | biostudies-arrayexpress
Project description:retroperitoneal liposarcoma TCR β CDR3 sequencing
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Project description:The origin and function of human double negative (DN) TCR-alpha/beta T cells is unknown. They are thought to contribute to the pathogenesis of systemic lupus erythematosus because they expand and accumulate in inflamed organs. Here we provide evidence that human TCR-alpha/beta CD4- CD8- DN T cells derive exclusively from activated CD8+ T cells. Freshly isolated TCR-alpha/beta DN T cells display a distinct gene expression and cytokine production profile. DN cells isolated from peripheral blood as well as DN cells derived in vitro from CD8+ T cells, produce a defined array of pro-inflammatory mediators that includes IL-1, IL-17, IFN-gama, CXCL3, and CXCL2. These results indicate that, upon activation, CD8+ T cells have the capacity to acquire a distinct phenotype that grants them inflammatory capacity. TCR-alpha-beta+ CD25- T cells from healthy human individuals were sorted into CD4+, CD8+, and CD4-CD8- T cells. Cell lysis and RNA extraction was performed immediately. RNA from each cell subset was pooled.
2009-05-16 | E-GEOD-16130 | biostudies-arrayexpress
Project description:Local administration of IFN-α-iPSC-pMCs alters gene expression profiles in tumor microenvironment.
| PRJNA521845 | ENA
Project description:The origin and function of human double negative (DN) TCR-alpha/beta T cells is unknown. They are thought to contribute to the pathogenesis of systemic lupus erythematosus because they expand and accumulate in inflamed organs. Here we provide evidence that human TCR-alpha/beta CD4- CD8- DN T cells derive exclusively from activated CD8+ T cells. Freshly isolated TCR-alpha/beta DN T cells display a distinct gene expression and cytokine production profile. DN cells isolated from peripheral blood as well as DN cells derived in vitro from CD8+ T cells, produce a defined array of pro-inflammatory mediators that includes IL-1, IL-17, IFN-gama, CXCL3, and CXCL2. These results indicate that, upon activation, CD8+ T cells have the capacity to acquire a distinct phenotype that grants them inflammatory capacity.
2009-05-16 | GSE16130 | GEO
Project description:Background: Anti-tumor immunity is highly heterogeneous between individuals; however, underlying mechanisms remain elusive, despite their potential to improve personalized cancer immunotherapy. Head and neck squamous cell carcinomas (HNSCCs) vary significantly in immune infiltration and therapeutic responses between patients, demanding a mouse model with appropriate heterogeneity to investigate mechanistic differences. Methods: We developed a unique HNSCC mouse model to investigate underlying mechanisms of heterogeneous anti-tumor immunity. This model system may provide a better control for tumor-intrinsic and host-genetic variables, thereby uncovering the contribution of the adaptive immunity to tumor eradication. We employed single-cell T-cell receptor (TCR) sequencing coupled with single-cell RNA sequencing to identify the difference in TCR repertoire of CD8 tumor infiltrating lymphocytes (TILs) and the unique activation states linked with different TCR clonotypes. Results: We discovered that genetically identical wild-type recipient mice responded heterogeneously to the same SCC tumors orthotopically transplanted into the buccal mucosa. While tumors initially grew in 100% of recipients and most developed aggressive tumors, ~25% of recipients reproducibly eradicated tumors without intervention. Heterogeneous anti-tumor responses were dependent on CD8 T cells. Consistently, CD8 TILs in regressing tumors were significantly increased and more activated. Single-cell TCR-sequencing revealed that CD8 TILs from both growing and regressing tumors displayed evidence of clonal expansion compared with splenic controls. However, top TCR clonotypes and TCR specificity groups appear to be mutually exclusive between regressing and growing TILs. Furthermore, many TCRa/TCRb sequences only occur in one recipient. By coupling single-cell transcriptomic analysis with unique TCR clonotypes, we found that top TCR clonotypes clustered in distinct activation states in regressing vs. growing TILs. Intriguingly, the few TCR clonotypes shared between regressors and progressors differed greatly in their activation states, suggesting a more dominant influence from tumor microenvironment than TCR itself on T cell activation status. Conclusions: We reveal that intrinsic differences in the TCR repertoire of TILs and their different transcriptional trajectories may underlie the heterogeneous anti-tumor immune responses in different hosts. We suggest that anti-tumor immune responses are highly individualized and different hosts employ different TCR specificities against the same tumors, which may have important implications for developing personalized cancer immunotherapy.
2021-01-13 | GSE164153 | GEO
Project description:The naïve polyclonal CD4 T cell repertoire can differentiate into multiple lineages during acute viral infection, with some T cell clones exhibiting a preferred lineage choice. TCR α CDR3 motifs can partially influence a clone-intrinsic lineage preference towards TFH fate.
2020-11-10 | GSE158896 | GEO
Project description:Emerging evidence suggests that an increased density of pre-treatment CD8+ tumor-infiltrating lymphocytes (TILs) is associated with good response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. However, the significance of T-cell complexity in the clinical setting remains unknown. High-throughput T-cell receptor (TCR) β sequencing was applied to quantify the TCR repertoire of pre-treatment biopsies from 67 patients with advanced rectal cancer receiving preoperative CRT. Changes in TCR repertoire before and after CRT were also analysed in 23 patients.
2022-11-22 | GSE218181 | GEO