Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1066390 | ENA |
REPOSITORIES: ENA
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Project description:Cellular metabolic status profoundly influences T cell differentiation, persistence, and anti-tumor efficacy. By performing single-cell metabolic analyses of T cells from human cancer and mouse chronic infection atlases, we unveiled that diminished mannose metabolism is a prominent feature of T cell dysfunction. Conversely, experimental augmentation/restoration of mannose metabolism in adoptively transferred T cells via D-mannose supplementation enhanced anti-tumor activity and restricted exhaustion differentiation both in vitro and in vivo. Mechanistically, D-mannose treatment induced intracellular metabolic programming and increased the O-GlcNAcylation of β-catenin, which preserved Tcf7 expression and epigenetic stemness, thereby promoting stem- like programs in T cells. Finally, in vitro expansion with mannose supplementation yielded T cell products for adoptive therapy with stemness characteristics, even after extensive long-term expansion, that exhibited enhanced anti-tumor efficacy. Thus, these findings reveal cell-intrinsic mannose metabolism as a physiological regulator of CD8+ T cell fate, decoupling proliferation/expansion from differentiation, and underscored the therapeutic potential of mannose modulation in cancer immunotherapy.
2025-01-01 | GSE254222 | GEO
Project description:Inactivation of tumor infiltrating lymphocytes (TILs) is one of the limiting factors of anti-tumor immunity during tumor onset and progression. Epigenetic abnormalities are regarded as a major culprit contributing to the dysfunction of TILs within tumor microenvironment. In this study, we used a murine model of melanoma to discover that Tet2 inactivation significantly enhances the anti-tumor activity of TILs, with the efficacy comparable to immune checkpoint inhibition imposed by anti-PD-L1 treatment. Single-cell RNA-seq analysis further reveals that Tet2-deficient TILs exhibit effector-like features. Transcriptomic and ATAC-seq analysis further demonstrated that Tet2 deletion reshapes the chromatin accessibility and favors the binding of transcription factors geared toward CD8+ T cell activation. In summary, our study establishes that Tet2 constitutes one of the epigenetic barriers contributing to dysfunction of TILs during anti-tumor immunity, and that Tet2 inactivation could benefit anti-tumor immunity and suppress tumor growth.
2021-04-20 | GSE152496 | GEO
Project description:Mounting evidence has highlighted the importance of complement in the construction of an immunosuppressive tumor microenvironment (TME). Tumor cell-derived C3 has been previously reported, however, whether and how it acts on anti-tumor immunity remains to be elucidated. Here, we describe a unique role of tumor cell-derived C3 in suppressing anti-tumor immunity. Tumor cell-derived C3 was activated intracellularly, which results in generation of C3a. C3a could modulate tumor-associated macrophages (TAMs) via C3a-C3aR-PI3Kγ signaling, thereby repressing anti-tumor immunity. More importantly, deletion of C3 in tumor cells with high C3 expression is sufficient to enhance the efficacy of ɑPD-L1 treatment. Collectively, our present results suggest tumor cell-derived C3 may serve as a novel target in cancer immunotherapy, specifically targeting C3 in tumor cells to enhance anti-tumor immunity.
2018-09-21 | GSE120274 | GEO
Project description:Metastasis-entrained eosinophils enhance lymphocyte-1 mediated anti-tumor immunity
| PRJNA752166 | ENA
Project description:Cryoablation reshapes the immune microenvironment in the distal tumor and enhances the anti-tumor immunity
| PRJNA832275 | ENA
Project description:Sirt2 Inhibition Reprograms T Cell Metabolism to Confer Superior Anti-Tumor Immunity
| PRJNA635802 | ENA
Project description:The immune system is our body’s defense mechanism, which helps us to resist foreign pathogens and cancer cells in the body. However, if the immune system is too weak, too strong, or unbalanced, it will be susceptible to get bacterial and viral infections, unable to fight cancer, or cause allergies, autoimmune and rheumatic diseases. At present, there is no good western medicine to strengthen immunity when the body is insufficient immunity. However, strong immunity causes autoimmune diseases and need to be treated by steroids and immunosuppressive agents. These drugs have limited efficacy and often have many side effects. In the clinical practice of traditional Chinese medicine, tonify qi, supplement blood and nourish yin are often used to enhance immunity. However, there is no clinical test to demonstrate the modulation of immune response after traditional Chinese medicine treatment.
In our preliminary study, the investigators identified that the basic immune response of cancer patients is weaker than healthy people by testing the level of IFN-r (promoting T cell activity, anti-tumor, anti-viral), TNF-a (promoting B cell proliferation, producing antibodies, anti-tumor, anti-viral) and IL-2 (regulate the proliferation and differentiation). Besides, some Chinese herbal extracts can significantly stimulate the immune response higher than the general average basic immunity of cancer patients. Further, we will use the stimulatory Chinese medicine extract to administer to cancer patients and examine the immune response of cancer patients after taking them. Therefore, this test can provide actual data on the basic immunity of healthy people or cancer patients and the modulation of immune response by traditional Chinese medicine treatment. This analysis platform provides patients to select the medicines that can enhance the immune response for individuals and analyze the changes of the immune response after conditioning with the candidate Chinese medicines. Therefore, this test could be applied clinically to validate the immunological regulation of Chinese herbal medicine as well as analyze the immunological modulation against different cancer by various Chinese herbal medicine.
| 2343085 | ecrin-mdr-crc
Project description:Antibodies targeting “immune checkpoints” have revolutionized cancer therapy by reactivating tumor-resident cytotoxic lymphocytes, primarily CD8 T cells. Interest in targeting analogous pathways in other cytotoxic lymphocytes is growing. Natural killer (NK) cells are key to cancer immunosurveillance by eradicating metastases and driving solid tumor inflammation. NK cell anti-tumor function is dependent on the cytokine interleukin (IL)-15. Ablation of the IL-15 signaling inhibitor CIS (Cish) enhances NK cell anti-tumor immunity by increasing NK cell metabolism and persistence within the tumor microenvironment (TME). The TME has also been shown to impair NK cell fitness via the production of immunosuppressive TGF-b, a suppression which occurs even in the presence of high IL-15 signaling. Here, we identified an unexpected interaction between CIS and the TGF-b signaling pathway in NK cells. Independently, Cish- and Tgfbr2- deficient NK cells are both hyper-responsive to IL-15 and hypo-responsive to TGF-b, with dramatically enhanced anti-tumor immunity. Remarkably, when both these immunosuppressive genes are simultaneously deleted in NK cells, mice are largely resistant to tumor development, suggesting that combining suppression of these two pathways might represent a novel therapeutic strategy to enhance innate anti-cancer immunity.
2022-04-11 | GSE200134 | GEO