Immune checkpoint blockade (ICB) has shown long‐term survival benefits, but only in a small fraction of cancer patients. Recent studies suggest that improved vessel perfusion by ICB positively correlates with its therapeutic outcomes. However, the underlying mechanism of such a process remains unclear. Here, we show that anti‐cytotoxic T‐lymphocyte‐associated protein 4 (CTLA4) treatment‐induced tumor vessel normalization was accompanied by an increased infiltration of eosinophils into breast tumors. Eosinophil accumulation was positively correlated with the responsiveness of a breast tumor to anti‐CTLA4 therapy. Depletion of eosinophils subsequently negated vessel normalization, reduced antitumor immunity and attenuated tumor growth inhibition by anti‐CTLA4 therapy. Moreover, intratumoral accumulation of eosinophils relied on T lymphocytes and interferon γ production. Together, these results suggest that eosinophils partially mediate the antitumor effects of CTLA4 blockade through vascular remodeling. Our findings uncover an unidentified role of eosinophils in anti‐CTLA4 therapy, providing a potential new target to improve ICB therapy and to predict its efficacy.

The immunosuppressive and hypoxic tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we showed that elevated levels of Delta-like 1 (DLL1) in the breast and lung TME induced long-term tumor vascular normalization to alleviate tumor hypoxia and promoted the accumulation of interferon γ (IFN-γ)–expressing CD8+ T cells and the polarization of M1-like macrophages. Moreover, increased DLL1 levels in the TME sensitized anti-cytotoxic T lymphocyte–associated protein 4 (anti-CTLA4) treatment in its resistant tumors, resulting in tumor regression and prolonged survival. Mechanically, in vivo depletion of CD8+ T cells or host IFN-γ deficiency reversed tumor growth inhibition and abrogated DLL1-induced tumor vascular normalization without affecting DLL1-mediated macrophage polarization. Together, these results demonstrate that elevated DLL1 levels in the TME promote durable tumor vascular normalization in a CD8+ T cell– and IFN-γ–dependent manner and potentiate anti-CTLA4 therapy. Our findings unveil DLL1 as a potential target to persistently normalize the TME to facilitate cancer immunotherapy.

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The utility-scale co-located hybrid power plants (HPPs) have been receiving attention globally due to enhanced controllability and efficient utilization of electrical infrastructure. While power plant control has been extensively studied for single-technology power plants in the past decades, how to control a co-located HPP that includes sub-plants with multiple technologies is yet to be well defined. To fill the gap, this paper proposes a novel hierarchical control architecture for co-located HPPs. This control architecture contains four control levels: asset control level, plant control level, HPP control level and HPP energy management system (EMS) level. The objective of HPP EMS level is to find optimal strategies for market participation, and the objective of HPP control level is to execute those strategies from the HPP EMS in real time. The interactions across the control hierarchy are firstly discussed in this paper, where attention is closely paid to interactions between HPP EMS level and HPP control level, and between HPP control level and plant control level. Novel strategies for control coordination are presented to ensure all the control levels work together without counteracting against each other. Frequency control and fault ride-through are two examples to demonstrate such control coordination.

Variability and uncertainties of wind and solar bring significant challenges into power system operation and control. Hybrid power plants (HPPs), which incorporates the complementary nature of wind and solar together with other technologies, such as energy storage, is a solution to cope with these challenges. To maximize the revenue and enable the operation of HPPs, the energy management system and the supervisory controller are both needed, namely the HPP EMS and the HPPC. The HPP EMS provides optimal dispatch strategies in order to maximize the revenue through market bids. Meanwhile, the HPPC executes dispatch plans from the HPP EMS in a real-time fashion. The paper highlights a new design of HPP EMS and HPPC with a focus on interface design between the two. The variables exchanged between the HPP EMS and the HPPC are presented, and practical issues such as time coordination and robustness over communication failure are discussed in detail.