Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

HDACs alters negatively to the tumor immune microenvironment in gynecologic cancers.

The role of histone deacetylases (HDACs) in the tumor immune microenvironment of gynecologic tumors remains unexplored. We integrated data from The Cancer Genome Atlas and Human Protein Atlas to examine HDAC expression in breast, cervical, ovarian, and endometrial cancers. Elevated HDAC expression correlated with poor prognosis and highly malignant cancer subtypes. Gene Set Enrichment Analysis revealed positive associations between HDAC expression and tumor proliferation signature, while negative associations were found with tumor inflammation signature. Increased HDAC expression was linked to reduced infiltration of natural killer (NK), NKT, and CD8+ T cells, along with negative associations with the expression of PSMB10, NKG7, CCL5, CD27, HLA-DQA1, and HLA-DQB1. In a murine 4T1 breast cancer model, treatment with suberoylanilide hydroxamic acid (SAHA; HDAC inhibitor) and PD-1 antibody significantly inhibited tumor growth and infiltration of CD3+ and CD8+ T cells. Real-time polymerase chain reaction revealed upregulated expressions of Psmb10, Nkg7, Ccl5, Cd8a, Cxcr6, and Cxcl9 genes, while Ctnnb1 and Myc genes were inhibited, indicating tumor suppression and immune microenvironment activation. Our study revealed that HDACs play tumor-promoting and immunosuppressive roles in gynecologic cancers, suggesting HDAC inhibitors as potential therapeutic agents for these cancers.

Regulating Lithium Plating and Stripping by Using Vertically Aligned Graphene/CNT Channels Decorated with ZnO Particles.

Lithium (Li) metal is regarded as the ultimate anode material for use in Li batteries due to its high theoretical capacity (3860 mA h g-1 ). However, the Li dendrites that are generated during iterative Li plating/stripping cycles cause poor cycling stability and even present safety risks, and thus severely handicap the commercial utility of Li metal anodes. Herein, we describe a graphene and carbon nanotube (CNT)-based Li host material that features vertically aligned channels with attached ZnO particles (designated ZnO@G-CNT-C) and show that the material effectively regulates Li plating and stripping. ZnO@G-CNT-C is prepared from an aqueous suspension of Zn(OAc)2 , CNTs, and graphene oxide by using ice to template channel growth. ZnO@G-CNT-C was found to be mechanically robust and capable of guiding Li deposition on the inner walls of the channels without the formation of Li dendrites. When used as an electrode, the material exhibits relatively low polarization for Li plating, fast Li-ion diffusion, and high Coulombic efficiency, even over hundreds of Li plating/stripping cycles. Moreover, full cells prepared with ZnO@G-CNT-C as Li host and LiFePO4 as cathode exhibit outstanding performance in terms of specific capacity (155.9 mA h g-1 at 0.5 C), rate performance (91.8 mA h g-1 at 4 C), cycling stability (109.4 mA h g-1 at 0.5 C after 800 cycles). The methodology described can be readily adapted to enable the use of carbon-based electrodes with well-defined channels in a wide range of contemporary applications that pertain to energy storage and delivery.

Expression of PAWR predicts prognosis of ovarian cancer.

BACKGROUND: Ovarian cancer greatly threatens the general health of women worldwide. Implementation of predictive prognostic biomarkers aids in ovarian cancer management. METHODS: Using online databases, the general expression profile, target-disease associations, and interaction network of PAWR were explored. To identify the role of PAWR in ovarian cancer, gene correlation analysis, survival analysis, and combined analysis of drug responsiveness and PAWR expression were performed. The predictive prognostic value of PAWR was further validated in clinical samples. RESULTS: PAWR was widely expressed in normal and cancer tissues, with decreased expression in ovarian cancer tissues compared with normal tissues. PAWR was associated with various cancers including ovarian cancer. PAWR formed a regulatory network with a group of proteins and correlated with several genes, which were both implicated in ovarian cancer and drug responsiveness. High PAWR expression denoted better survival in ovarian cancer patients (OS: HR = 0.84, P = 0.0077; PFS, HR = 0.86, P = 0.049). Expression of PAWR could predict platinum responsiveness in ovarian cancer and there was a positive correlation between PAWR gene effect and paclitaxel sensitivity. In 12 paired clinical samples, the cancerous tissues exhibited significantly lower PAWR expression than matched normal fallopian tubes. The predictive prognostic value of PAWR was maintained in a cohort of 50 ovarian cancer patients. CONCLUSIONS: High PAWR expression indicated better survival and higher drug responsiveness in ovarian cancer patients. PAWR could be exploited as a predictive prognostic biomarker in ovarian cancer.