Characteristics of a CCL21-gene modified dendritic cell vaccine utilized for a clinical trial in non-small cell lung cancer.

The treatment of non-small cell lung cancer has made major strides with the use of immune checkpoint inhibitors, but there remains a significant need for therapies that can overcome immunotherapy resistance. Dendritic cell (DC) vaccines have been proposed as a therapy that can potentially enhance the antitumor immune response. We have embarked on a phase I clinical trial of a vaccine consisting of monocyte-derived DCs (moDCs) modified to express the chemokine CCL21 (CCL21-DC) given in combination with pembrolizumab.

Effect of Solvent and Cholesterol on Liposome Production by the Reverse-Phase Evaporation (RPE) Method.

Liposomal drug delivery is a promising approach for delivering therapeutics effectively. While most liposomes are designed to be nanometer-sized for efficient cellular uptake, micron-sized liposomes are gaining interest due to their larger drug-loading capacity. When combined with macroscale structures, such as implants and hydrogels, they offer prolonged therapeutic delivery.

CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer.

Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T cell recruitment and ICB resistance.

Experience of Autologous Immunotherapy for Non-Small Cell Lung Cancer Using Zoledronate-Actived Gammadelta T Cells.

Background: Several nations around the world have utilized autologous immune enhancement therapy in the treatment of cancer, with initial positive outcomes. This study describes our experience with autologous gamma delta T cell immunotherapy for the treatment of non-small cell lung cancer patients in Vietnam, a developing nation.

Methods: Five patients with non-small cell lung cancer at stages III - IV were enrolled in the study.

CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity.

Background: Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation.

Serum CA-125 as a predictor in the early diagnosis of ectopic pregnancy in Vietnam - A case-control study.

Introduction: This study aimed to determine the predictive value of cancer antigen-125 (CA-125) in combination with serum beta-human chorionic gonadotropin (β-hCG) and progesterone in the early detection of ectopic pregnancy (EP).

Methods: Between May 2019 and May 2020, the cross-sectional study recruited 42 cases of EP and 42 cases of IUP at the same gestational age who visited the Department of Obstetrics and Gynecology, Hospital of Hue University of Medicine and Pharmacy. EP was diagnosed based on surgical (laparoscopy) and postoperative pathology examination.

Single-Cell Characterization of Pulmonary Nodules Implicates Suppression of Immunosurveillance across Early Stages of Lung Adenocarcinoma.

Unlabelled: A greater understanding of molecular, cellular, and immunological changes during the early stages of lung adenocarcinoma development could improve diagnostic and therapeutic approaches in patients with pulmonary nodules at risk for lung cancer. To elucidate the immunopathogenesis of early lung tumorigenesis, we evaluated surgically resected pulmonary nodules representing the spectrum of early lung adenocarcinoma as well as associated normal lung tissues using single-cell RNA sequencing and validated the results by flow cytometry and multiplex immunofluorescence (MIF). Single-cell transcriptomics revealed a significant decrease in gene expression associated with cytolytic activities of tumor-infiltrating natural killer and natural killer T cells.

A case of response to combination treatment with autologous immunotherapy and bevacizumab in advanced non-small cell lung cancer.

Natural killer (NK) cells have developed as a potent tool in cancer immunotherapy. Especially, patients who have failed in the first-line or maintenance treatment received a good response with immunotherapy in association with other approaches. We report the case of a 61-year-old male patient with programmed cell death ligand - 1(PD-L1) expression in advanced non-small cell lung cancer (NSCLC) (stage IV).

Associated factors with Premenstrual syndrome and Premenstrual dysphoric disorder among female medical students: A cross-sectional study.

Aim: The study aimed to determine potential risk factors associated with Premenstrual Syndrome and Premenstrual Dysphoric Disorder.

Methods: Three hundred two female student participants who were 18-45 years old completed a questionnaire including demographic characteristics, lifestyle factors, and a Vietnamese Premenstrual Syndrome Screening Tool. We then followed up participants during at least two menstrual cycles using the Daily Record of Severity of Problems.

Aerobic vaginitis in the third trimester and its impact on pregnancy outcomes.

Background: Aerobic vaginitis (AV) is a vaginal inflammation characterized by disruption of the lactobacillus microbiota and increased counts of different aerobic bacteria. AV may result in severe complications, especially during pregnancy, including preterm delivery, neonatal and maternal infections. This study aimed to determine the prevalence of AV in the third trimester of pregnancy, and the relationship between AV and pregnancy outcomes.

Genotoxic Treatment Enhances Immune Response in a Genetic Model of Lung Cancer.

Recent advances in immunotherapy have reshaped the clinical management of lung cancer, and immune checkpoint inhibitors (ICIs) are now first-line treatment for advanced lung cancer. However, the majority of patients do not respond to ICIs as single agents, and many develop resistance after initial responses. Therefore, there is urgent need to improve the current ICI strategies.

Early Diagnosis and Screening for Lung Cancer.

Cancer interception refers to actively blocking the cancer development process by preventing progression of premalignancy to invasive disease. The rate-limiting steps for effective lung cancer interception are the incomplete understanding of the earliest molecular events associated with lung carcinogenesis, the lack of preclinical models of pulmonary premalignancy, and the challenge of developing highly sensitive and specific methods for early detection. Recent advances in cancer interception are facilitated by developments in next-generation sequencing, computational methodologies, as well as the renewed emphasis in precision medicine and immuno-oncology.

Health Savings Plans and Disparities in Access to Care by Race and Ethnicity.

Introduction: High-deductible health plans are often touted to motivate patients to become informed healthcare purchasers; however, racial/ethnic minorities report that high deductibles prevent them from seeking the needed care. One proposed way to mitigate the financial burden of high-deductible health plans is the use of health savings plans. This cross-sectional study investigates whether chronically ill Blacks and Hispanics enrolled in high-deductible health plans experience greater access to care difficulties than non-Hispanic Whites and whether racial/ethnic disparities are mitigated by the use of health savings plans.

Resolving the Spatial and Cellular Architecture of Lung Adenocarcinoma by Multiregion Single-Cell Sequencing.

Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing of 186,916 cells from five early-stage LUADs and 14 multiregion normal lung tissues of defined spatial proximities from the tumors. We show that cellular lineages, states, and transcriptomic features geospatially evolve across normal regions to LUADs.

Inhibition of Granulocytic Myeloid-Derived Suppressor Cells Overcomes Resistance to Immune Checkpoint Inhibition in LKB1-Deficient Non-Small Cell Lung Cancer.

LKB1 inactivating mutations are commonly observed in patients with KRAS-mutant non-small cell lung cancer (NSCLC). Although treatment of NSCLC with immune checkpoint inhibitors (ICI) has resulted in improved overall survival in a subset of patients, studies have revealed that co-occurring KRAS/LKB1 mutations drive primary resistance to ICIs in NSCLC. Effective therapeutic options that overcome ICI resistance in LKB1-mutant NSCLC are limited.

Novel Kras-mutant murine models of non-small cell lung cancer possessing co-occurring oncogenic mutations and increased tumor mutational burden.

Conditional genetically engineered mouse models (GEMMs) of non-small cell lung cancer (NSCLC) harbor common oncogenic driver mutations of the disease, but in contrast to human NSCLC these models possess low tumor mutational burden (TMB). As a result, these models often lack tumor antigens that can elicit host adaptive immune responses, which limits their utility in immunotherapy studies. Here, we establish Kras-mutant murine models of NSCLC bearing the common driver mutations associated with the disease and increased TMB, by in vitro exposure of cell lines derived from GEMMs of NSCLC [Kras (K), KrasTp53(KP), KrasTp53Lkb1 (KPL)] to the alkylating agent N-methyl-N-nitrosourea (MNU).

Immunosurveillance and Regression in the Context of Squamous Pulmonary Premalignancy.

In this issue of , Pennycuick and colleagues comprehensively evaluate the immune contexture of progressive and regressive lesions in squamous pulmonary premalignancy. The authors dissect the molecular features of these lesions and the potential pathways of immune escape operative in progression to invasive cancer..

Author Correction: Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent a gradually progressing epithelial-to-mesenchymal (EMT) phenotype following a 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for lung cancer pulmonary and the lung tumor microenvironments. Pathway analysis of the gene expression profile and in vitro functional studies revealed that the EMT and EMT-associated phenotypes, including enhanced cell invasion, PD-L1 upregulation, and chemoresistance, were sustained in the absence of continuous IL-1β exposure.

The Immune Contexture Associates with the Genomic Landscape in Lung Adenomatous Premalignancy.

Epithelial cells in the field of lung injury can give rise to distinct premalignant lesions that may bear unique genetic aberrations. A subset of these lesions may escape immune surveillance and progress to invasive cancer; however, the mutational landscape that may predict progression has not been determined. Knowledge of premalignant lesion composition and the associated microenvironment is critical for understanding tumorigenesis and the development of effective preventive and interception strategies.

Silencing the Snail-Dependent RNA Splice Regulator ESRP1 Drives Malignant Transformation of Human Pulmonary Epithelial Cells.

Epithelial-to-mesenchymal transition (EMT) is organized in cancer cells by a set of key transcription factors, but the significance of this process is still debated, including in non-small cell lung cancer (NSCLC). Here, we report increased expression of the EMT-inducing transcription factor Snail in premalignant pulmonary lesions, relative to histologically normal pulmonary epithelium. In immortalized human pulmonary epithelial cells and isogenic derivatives, we documented Snail-dependent anchorage-independent growth and primary tumor growth and metastatic behavior Snail-mediated transformation relied upon silencing of the tumor-suppressive RNA splicing regulatory protein ESRP1.