Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity.

Regulatory T (Treg) cells are critical for immune tolerance but also form a barrier to antitumor immunity. As therapeutic strategies involving Treg cell depletion are limited by concurrent autoimmune disorders, identification of intratumoral Treg cell-specific regulatory mechanisms is needed for selective targeting. Epigenetic modulators can be targeted with small compounds, but intratumoral Treg cell-specific epigenetic regulators have been unexplored. Here, we show that JMJD1C, a histone demethylase upregulated by cytokines in the tumor microenvironment, is essential for tumor Treg cell fitness but dispensable for systemic immune homeostasis. JMJD1C deletion enhanced AKT signals in a manner dependent on histone H3 lysine 9 dimethylation (H3K9me2) demethylase and STAT3 signals independently of H3K9me2 demethylase, leading to robust interferon-γ production and tumor Treg cell fragility. We have also developed an oral JMJD1C inhibitor that suppresses tumor growth by targeting intratumoral Treg cells. Overall, this study identifies JMJD1C as an epigenetic hub that can integrate signals to establish tumor Treg cell fitness, and we present a specific JMJD1C inhibitor that can target tumor Treg cells without affecting systemic immune homeostasis.

Multistatic Integrated Sensing and Communication System Based on Macro-Micro Cooperation.

A novel multistatic integrated sensing and communication (ISAC) system based on macro-micro cooperation for the sixth-generation (6G) mobile network is proposed. Instead of using macrosites at both the transmitter and receiver sides, microsites are considered as receivers in cooperative sensing. This system is important since microsites can be deployed more flexibly to reduce their distances to the sensing objects, providing better coverage for sensing service. In this work, we first analyze the deployment problem of microsites, which can be deployed along the radius and azimuth angle to cover macrosite cells. The coverage area of each microsite is derived in terms of its position in the cell. Then, we describe an efficient estimating approach for obtaining the position and velocity of sensing objects in the macrosite cell. By choosing multiple microsites around the targeted sensing area, joint data processing with an efficient optimization method is also provided. Simulation results show that the multistatic ISAC system employing macro-micro cooperation can improve the position and velocity estimation accuracy of objects compared to systems employing macrosite cooperation alone, demonstrating the effectiveness and potential for implementing the proposed system in the 6G mobile network.