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CD45 sequestration lowers the signaling threshold in lymphocytes and enhances anti-tumor immunity

ABSTRACT: CD45 sequestration lowers the signaling threshold in lymphocytes and enhances anti-tumor immunity

PROVIDER: PRJNA1290926 | ENA |

REPOSITORIES: ENA

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CD45 sequestration lowers the signaling threshold in lymphocytes and enhances anti-tumor immunity

Project description:CD45 plays a central role in immune signal regulation by controlling the spatial dynamics of phosphatase activity through steric segregation of its bulky rigid extracellular domain. To modulate CD45 activity, here we develop and characterize protein engineering approaches to induce multivalent clustering of CD45, effectively mimicking the endogenous local receptor sequestration during immune synapse formation. In doing so, we engineer a biologic that enables precise, tunable control over CD45 surface localization and activity. CD45 sequestration exhibited striking synergy when administered in combination with intratumorally anchored IL-12 therapy, markedly delaying tumor progression and extending survival in syngeneic murine melanoma and carcinoma models. Immune profiling revealed that CD8⁺ T cells are essential mediators of this synergistic antitumor response. Mechanistically, IL-12 initiates a wave of antigen generation and T cell priming, while CD45 sequestration subsequently enhances tumor-specific CD8⁺ T cell activation, expansion, and functional states within the tumor-draining lymph node. These findings suggest that CD45 sequestration lowers the activation threshold of T cells, broadens the tumor-reactive T cell repertoire, and therefore promotes more robust tumor-specific T cell responses. Altogether, we establish CD45 as a promising novel target for cancer immunotherapy, capable of potentiating strong anticancer immune responses.

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CD45+ vs CD45- RCC proteome characterization

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Transcription profiling of mouse CD45- and CD45+ cells in the embryonic lung

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Deoxygenation lowers the thermal threshold of coral bleaching.

Project description:Exposure to deoxygenation from climate warming and pollution is emerging as a contributing factor of coral bleaching and mortality. However, the combined effects of heating and deoxygenation on bleaching susceptibility remain unknown. Here, we employed short-term thermal stress assays to show that deoxygenated seawater can lower the thermal limit of an Acropora coral by as much as 1 °C or 0.4 °C based on bleaching index scores or dark-acclimated photosynthetic efficiencies, respectively. Using RNA-Seq, we show similar stress responses to heat with and without deoxygenated seawater, both activating putative key genes of the hypoxia-inducible factor response system indicative of cellular hypoxia. We also detect distinct deoxygenation responses, including a disruption of O2-dependent photo-reception/-protection, redox status, and activation of an immune response prior to the onset of bleaching. Thus, corals are even more vulnerable when faced with heat stress in deoxygenated waters. This highlights the need to integrate dissolved O2 measurements into global monitoring programs of coral reefs.

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Analysis of transcriptional differences between TER cells, B lymphocytes and embryonic liver nucleated erythrocytes

Project description:To verify the origin of TER cells from B lymphocytes，we profiled the differentially expressed genes in CD19+/TER119+/CD45+ cells by RNA-sequencing, with fetal liver-derived CD71+/TER119+/FSChigh cells (CECs) as erythroblast control and CD19+/TER119- cells as B-cell control.

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Project description:Ablation of Hepatic CPT1a Lowers Plasma Cholesterol Levels

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Ablation of Hepatic CPT1a Lowers Plasma Cholesterol Levels.

Project description:Ablation of Hepatic CPT1a Lowers Plasma Cholesterol Levels.

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Gene expression profiling and localization of Hoechst-effluxing CD45- and CD45+ cells in the Embryonic Mouse Lung

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