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Gene exprsesion profile at single cell level of CD45+ immune cells from 4TO7 cells (Ctrl or Tim3-KD) liver metastasis at different timepoints

ABSTRACT: Gene exprsesion profile at single cell level of CD45+ immune cells from 4TO7 cells (Ctrl or Tim3-KD) liver metastasis at different timepoints

PROVIDER: PRJNA1081867 | ENA |

REPOSITORIES: ENA

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Gene exprsesion profile at single cell level of CD45+ immune cells from 4TO7 cells (Ctrl or Tim3-KD) liver metastasis at different timepoints

Project description:In this study we describe the immunosupressive role of Tim3+ tumor cells during eraly stages of metastasis. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of immune cells subsets altered by Tim3 expression in the tumor cells. The aim was to determine the immune status of immunosuppressive and cytotoxic populations during the dynamic process of the metastatic colonization in the liver

2025-07-02 | GSE260482 | GEO

CD45+ vs CD45- RCC proteome characterization

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Tumor-activating IL2 rejuvenates intratumoral TIM3-CD8+T cell responses through targeting TIM3+CD8+T cell

Project description:TIM3, a T-cell inhibitory receptor, is expressed on exhausted T cells in tumor microenvironment (TME). Anti-TIM3 antibody therapy could alleviate the suppression of tumor-infiltrating lymphocytes (TILs) in IL-2 dependent fashion. We hypothesize that high expression of TIM3 and limited IL-2 in TME facilitate immune evasion. To test that, we engineered anti-TIM3-pro-IL2 to selectively deliver IL-2 to TIM3high TILs by TIM3 antibody and reduce its toxicity with a cis delivery mechanism. Since IL-2 could reduce its activity at acidic pH inside TME, we also screened a low pH-selective IL-2 mutein (IL2V2) with enhanced affinity for IL-2Rβ. We then integrated pro-IL-2 into the anti-TIM3 antibodies in two different forms: TIM3-Rα-MMPs-IL2V2 (TIM3-ProIL2V2) as IL-2 release-form vs TIM3-IL2V2-MMPs-Rα as cis-form after binding to TIM3high T cells, ensuring the need of targeted delivery to TIM3-expressing TILs. Surprisingly, released IL2V2 from TIM3-Rα-MMPs-IL2V2 proved superior in anti-tumor immunity, but not cis delivery form TIM3-IL2V2-MMPs-Rα. Mechanistically, TIM3-ProIL2V2 not only reactivated TIM3+ TILs but also facilitated the activation and expansion of TIM3- T cells which in turn supported a sustained source of TIM3+ effector. TIM3-ProIL2V2 could control multiple tumor models including human tumor in humanized mice, confirming the hypothesis. TIM3-ProIL2V2 activates and expands TIM3-CD8+ T cells to overcome current major unmet medical need: anti-PD-1/L1 resistance. This strategy illustrates the potential of a tailored, low pH-resistant IL2 variant in invigorating both TIM3-negative and positive CD8+ T cells, offering a promising avenue for treating resistant tumors with reduced toxicity.

2025-05-22 | GSE296919 | GEO

In vivo study of the Tim3-loss in breast cancer cells during metastasis

Project description:In metastasis, the existence tumor cells overcoming the immune system during early organ seeding is crucial, yet the dynamics of tumor-immune interactions during micrometastasis remain unclear. Examining the immune selective pressure in breast cancer (BC) mouse models, we unexpectedly found TIM3 among the most upregulated genes in metastatic surviving BC cells. The selection of TIM3+ tumor cells, was specifically occurring during early seeding of micrometastasis, escaping the immune attack and acquiring stemness. Also clinical data confirmed increased TIM3+ tumor cells in BC metastasis. The aim of the study was to understand the mechanistic insgihts of Tim3 in breast cancer cells in vivo to decipher pivotal pathways of Tim3-mediated immun-evasion.

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Timepoints 5073 strain

Project description:6 Timepoints from 5073 strain Keywords: Timepoints 5073 cwo

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Project description:Single-cell transcriptome analysis of tumor infiltrated CD45+ immune cells isolated from ctrl- or thonzonium bromide- treated mice

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Maternal Schistosomiasis CD45+

Project description:Maternal Schistosomiasis CD45+

| PRJNA680505 | ENA

Timepoints Control strain

Project description:6 Timepoint microarray from control strain Keywords: Timepoints yw

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