Cuproptosis, an emerging form of programmed cell death, has received tremendous attention in cancer therapy. However, the efficacy of cuproptosis remains limited by the poor delivery efficiency of copper ion carriers. Herein, copper complex nanoparticles (denoted as Cu(I) NP) are developed that can efficiently deliver copper complex into cancer cells to induce cuproptosis. Cu(I) NP demonstrate stimulus‐responsive release of copper complexes, which results in mitochondrial dysfunction and promotes the aggregation of lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), leading to cuproptosis. Notably, Cu(I) NP not only induce cuproptosis, but also elicit robust immune responses to suppress tumor growth. Overall, this study provides a promising strategy for cuproptosis‐based cancer therapy.

Regulatory T (Treg) cells are known to impede antitumor immunity, yet the regulatory mechanisms and functional roles of these cells remain poorly understood. In this study, through the characterization of multiple cancer models, we identified a substantial presence of peripherally induced Treg cells in the tumor microenvironment (TME). Depletion of these cells triggered antitumor responses and provided potent therapeutic effects by increasing functional CD8+ T cells. Fate-mapping and transfer experiments revealed that IFN-γ–expressing T helper (Th) 1 cells differentiated into Treg cells in response to TGF-β signaling in tumors. Pseudotime trajectory analysis further revealed the terminal differentiation of Th1-like Treg cells from Th1 cells in the TME. Tumor-resident Treg cells highly expressed T-bet, which was essential for their functions in the TME. Additionally, CD39 was highly expressed by T-bet+ Treg cells in both mouse and human tumors, and was necessary for Treg cell-mediated suppression of CD8+ T cell responses. Our study elucidated the developmental pathway of intratumoral Treg cells and highlighted novel strategies for targeting them in cancer patients.

Background: Preoperative differentiation of malignant and premalignant gallbladder polyps (GBPs) from benign lesions is a key imperative to guide treatment decision-making. We aimed to characterize the various types of GBPs and sought to identify the risk factors for neoplastic polyps. Our findings may help optimize treatment strategy. Methods: Retrospective analysis of 686 patients with post-cholecystectomy pathologically-proven GBPs between January 2003 and December 2016. The patients were classified into non-neoplastic polyp group, benign neoplastic polyp group, and adenoma canceration group. Clinical features, ultrasound findings, and results of laboratory investigations and histopathological examination were reviewed and compared between the groups. Results: Out of 686 patients, 542 (79.0%) had non-neoplastic polyps, 134 (19.5%) had neoplastic polyps, and 10 (1.5%) had adenoma canceration. The mean age was 46.06±12.12 years; 383 (55.8%) patients were female. The median (25^th percentile, 75^th percentile) time between diagnosis and surgery in the cholesterol polyp group [24 (3.5, 60) months] was significantly longer than that in adenoma [12 (2, 60) months] and adenoma canceration [5 (0.475, 12) months] groups. The mean diameter was 1.14±0.61 cm (range, 0.5–8.4 cm). Three hundred twelve (45.5%) patients had solitary polyps and intralesional blood flow was observed in 41 (6.0%) patients. On univariate analysis, age >49.5 years, polyp size >1.15 cm, solitary polyp, intralesional blood flow, absence of symptoms, and lack of cholecystitis showed a significant association with adenoma. On multivariate analysis, polyp size (>1.15 cm), intralesional blood flow, and lack of cholecystitis were independent predictors of adenoma. Conclusions: Polyp size >1.15 cm, intralesional blood flow, and lack of cholecystitis were predictors of neoplastic polyps. Malignant transformation of adenoma may occur over a relatively short time.