Long-range deployment of tumor-antigen-specific cytotoxic T lymphocytes inhibits lung metastasis of breast cancer.

Tumor-antigen-specific CD8 T cells (CTLs) are the main effector immunocytes in anti-tumor immunity, but their systemic deployment against cancer metastasis remains uncharacterized. Here, we found that the abundance of tumor-specific CD103CD8 T cells in the tumor-draining lymph nodes (TDLNs) was associated with improved lung-metastasis-free survival in breast cancer patients. In mouse cancer models, CD103CD8 T cells were primed in TDLNs and recruited to the lungs via C-C motif chemokine ligand 5/receptor 9 (CCL25/CCR9) signaling to inhibit metastasis through antigen-specific immunity.

Tumor-Associated Sympathetic Nerves Promote the Progression of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma.

Epstein-Barr virus-positive (EBV) diffuse large B-cell lymphoma (DLBCL) exhibits a poorer prognosis with limited treatment options. Although recent evidence indicates that the peripheral nervous system is associated with tumor progression, its role in EBVDLBCL remains poorly understood. In the cohort, patients with EBV⁺DLBCL exhibit significantly shorter overall survival (OS).

Cardiomyocyte-localized CCDC25 senses NET DNA to promote doxorubicin cardiotoxicity by activating autophagic flux.

Cardiotoxicity restricts the clinical use of anthracyclines. Although recent evidence indicates that aberrant activation of the cytosolic DNA-sensing pathway mediates cardiotoxicity, the function of extracellular DNA remains unclear. Here we observe a substantial increase in circulating neutrophil extracellular trap (NET) DNA in individuals with lymphoma experiencing cardiotoxicity after anthracycline-containing treatment.

The NET-DNA-CCDC25 inhibitor di-Pal-MTO suppresses tumor progression and promotes the innate immune response.

The DNA component of neutrophil extracellular traps (NET-DNA) is associated with cancer metastasis and chemotherapy resistance. However, recent studies have suggested that NET-DNA contributes to the activation of dendritic cells (DCs) and promotes the innate immune response to anticancer immunity. Therefore, exploring therapeutic approaches to inhibit NET-mediated tumor progression while maintaining antitumor immunity is essential.

Targeting NETosis: nature's alarm system in cancer progression.

Neutrophils are recognized active participants in inflammatory responses and are intricately linked to cancer progression. In response to inflammatory stimuli, neutrophils become activated, releasing neutrophils extracellular traps (NETs) for the capture and eradication of pathogens, a phenomenon termed NETosis. With a deeper understanding of NETs, there is growing evidence supporting their role in cancer progression and their involvement in conferring resistance to various cancer therapies, especially concerning tumor reactions to chemotherapy, radiation therapy (RT), and immunotherapy.

Activation of Bivalent Gene POU4F1 Promotes and Maintains Basal-like Breast Cancer.

Basal-like breast cancer (BLBC) is the most aggressive molecular subtype of breast cancer with worse prognosis and fewer treatment options. The underlying mechanisms upon BLBC transcriptional dysregulation and its upstream transcription factors (TFs) remain unclear. Here, among the hyperactive candidate TFs of BLBC identified by bioinformatic analysis, POU4F1 is uniquely upregulated in BLBC and is associated with poor prognosis.

CD8+ T cell-Dependent Remodeling of the Tumor Microenvironment Overcomes Chemoresistance.

The therapeutic efficacy of chemotherapy is in part a result of its ability to enhance adaptive antitumor immune responses. However, tumor cells exploit various evasion mechanisms to escape the immune attack and blunt chemosensitivity. Herein, we report that through single-cell profiling of the tumor immune microenvironment, we identified a subset of CD161-overexpressing CD8+ T cells enriched in chemoresistant tumors.

The IRENA lncRNA converts chemotherapy-polarized tumor-suppressing macrophages to tumor-promoting phenotypes in breast cancer.

Although chemotherapy can stimulate antitumor immunity by inducing interferon (IFN) response, the functional role of tumor-associated macrophages in this scenario remains unclear. Here, we found that IFN-activated proinflammatory macrophages after neoadjuvant chemotherapy enhanced antitumor immunity but promoted cancer chemoresistance. Mechanistically, IFN induced expression of cytoplasmic long noncoding RNA IFN-responsive nuclear factor-κB activator (IRENA) in macrophages, which triggered nuclear factor-κB signaling via dimerizing protein kinase R and subsequently increased production of protumor inflammatory cytokines.

Targeting regulator of G protein signaling 1 in tumor-specific T cells enhances their trafficking to breast cancer.

Reduced infiltration of anti-tumor lymphocytes remains a major cause of tumor immune evasion and is correlated with poor cancer survival. Here, we found that upregulation of regulator of G protein signaling (RGS)1 in helper T1 cells and cytotoxic T lymphocytes (CTLs) reduced their trafficking to and survival in tumors and was associated with shorter survival of patients with breast and lung cancer. RGS1 was upregulated by type II interferon (IFN)-signal transducer and activator of transcription (STAT)1 signaling and impaired trafficking of circulating T cells to tumors by inhibiting calcium influx and suppressing activation of the kinases ERK and AKT.

DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25.

Neutrophil extracellular traps (NETs), which consist of chromatin DNA filaments coated with granule proteins, are released by neutrophils to trap microorganisms. Recent studies have suggested that the DNA component of NETs (NET-DNA) is associated with cancer metastasis in mouse models. However, the functional role and clinical importance of NET-DNA in metastasis in patients with cancer remain unclear.

Tumor-Contacted Neutrophils Promote Metastasis by a CD90-TIMP-1 Juxtacrine-Paracrine Loop.

Purpose: The different prognostic values of tumor-infiltrating neutrophils (TIN) in different tissue compartments are unknown. In this study, we investigated their different prognostic roles and the underlying mechanism. We evaluated CD66b neutrophils in primary tumors from 341 patients with breast cancer from Sun Yat-sen Memorial Hospital by IHC.

Neutrophil Extracellular Traps Induced by IL8 Promote Diffuse Large B-cell Lymphoma Progression via the TLR9 Signaling.

Purpose: More than 30% of patients with diffuse large B-cell lymphoma (DLBCL) experience treatment failure after first-line therapy. Neutrophil extracellular traps (NETs), a pathogen-trapping structure in tumor microenvironment, can promote the transition of autoimmunity to lymphomagenesis. Here, we investigate whether NETs play a novel role in DLBCL progression and its underlying mechanism.

NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation-induced cell death.

Activation-induced cell death (AICD) of T lymphocytes can be exploited by cancers to escape immunological destruction. We demonstrated that tumor-specific cytotoxic T lymphocytes (CTLs) and type 1 helper T (T1) cells, rather than type 2 helper T cells and regulatory T cells, were sensitive to AICD in breast and lung cancer microenvironments. NKILA, an NF-κB-interacting long noncoding RNA (lncRNA), regulates T cell sensitivity to AICD by inhibiting NF-κB activity.

LncRNA NKILA suppresses TGF-β-induced epithelial-mesenchymal transition by blocking NF-κB signaling in breast cancer.

TGF-β plays a central role in mediating epithelial-mesenchymal transition (EMT) by activating the Smad pathway. In addition, accumulating evidence suggests that TGF-β-induced EMT is NF-κB-dependent in various cancer types. However, it is largely unclear if NF-κB mediates TGF-β-induced EMT in breast cancer, and if this mediation occurs, the regulatory mechanisms are unknown.

A serum microRNA signature predicts trastuzumab benefit in HER2-positive metastatic breast cancer patients.

Trastuzumab is a standard treatment for HER2-positive (HER2) breast cancer, but some patients are refractory to the therapy. MicroRNAs (miRNAs) have been used to predict therapeutic effects for various cancers, but whether miRNAs can serve as biomarkers for HER2 metastatic breast cancer (MBC) patients remains unclear. Using miRNA microarray, we identify 13 differentially expressed miRNAs in the serum of HER2 MBC patients with distinct response to trastuzumab, and four miRNAs are selected to construct a signature to predict survival using LASSO model.

CD10GPR77 Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness.

Carcinoma-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in tumor microenvironment that are critically involved in cancer progression. Here, we demonstrate that two cell-surface molecules, CD10 and GPR77, specifically define a CAF subset correlated with chemoresistance and poor survival in multiple cohorts of breast and lung cancer patients. CD10GPR77 CAFs promote tumor formation and chemoresistance by providing a survival niche for cancer stem cells (CSCs).

Production of 2,3-butanediol from acid hydrolysates of Jatropha hulls with Klebsiella oxytoca.

Jatropha hulls were successfully for the first time used as raw materials for the production of 2,3-butanediol via dilute sulfuric acid hydrolysis and fermentation with Klebsiella oxytoca. Two-step hydrolysis was used to effectively hydrolyze the hulls at 150°C after pretreatment. In the first-step, hemicellulose was hydrolyzed under mild conditions (0.

Pure natural orifice translumenal endoscopic surgery management of simple renal cysts: 2-year follow-up results.

Background And Purpose: Retrograde ureteroscopic marsupialization is a pure natural orifice translumenal endoscopic surgery (NOTES). We retrospectively examined the feasibility and safety of this technique to manage symptomatic simple renal cysts.

Patients And Methods: Sixteen patients with simple renal cysts were selected and treated by incising the cyst wall to drain into the collecting system through retrograde ureteroscopy.