Augmentation of tumor expression of HLA-DR, CXCL9, and CXCL10 may improve olfactory neuroblastoma immunotherapeutic responses.

BACKGROUND: Olfactory neuroblastoma is a rare malignancy of the anterior skull base typically treated with surgery and adjuvant radiation. Although outcomes are fair for low-grade disease, patients with high-grade, recurrent, or metastatic disease oftentimes respond poorly to standard treatment methods. We hypothesized that an in-depth evaluation of the olfactory neuroblastoma tumor immune microenvironment would identify mechanisms of immune evasion in high-grade olfactory neuroblastoma as well as rational targetable mechanisms for future translational immunotherapeutic approaches. METHODS: Multispectral immunofluorescence and RNAScope evaluation of the tumor immune microenvironment was performed on forty-seven clinically annotated olfactory neuroblastoma samples. A retrospective chart review was performed and clinical correlations assessed. RESULTS: A significant T cell infiltration was noted in olfactory neuroblastoma samples with a stromal predilection, presence of myeloid-derived suppressor cells, and sparse natural killer cells. A striking decrease was observed in MHC-I expression in high-grade olfactory neuroblastoma compared to low-grade disease, representing a mechanism of immune evasion in high-grade disease. Mechanistically, the immune effector stromal predilection appears driven by low tumor cell MHC class II (HLA-DR), CXCL9, and CXCL10 expression as those tumors with increased tumor cell expression of each of these mediators correlated with significant increases in T cell infiltration. CONCLUSION: These data suggest that immunotherapeutic strategies that augment tumor cell expression of MHC class II, CXCL9, and CXCL10 may improve parenchymal trafficking of immune effector cells in olfactory neuroblastoma and augment immunotherapeutic responses.

Comprehensive comparative analysis of the periodontal pathogen Porphyromonas gingivalis: exploring the pan-genome, the reconstruction of the gene regulatory network and genome-scale metabolic network.

Porphyromonas gingivalis is a nonmotile, obligate anaerobic, Gram-negative bacterium known for its association with periodontal disease and its involvement in systemic diseases such as atherosclerosis, cardiovascular disease, colon cancer, and Alzheimer's disease. This bacterium produces several virulence factors, including capsules, fimbriae, lipopolysaccharides, proteolytic enzymes, and hemagglutinins. A comparative genomic analysis revealed the open pangenome of P. gingivalis and identified complete type IV secretion systems in strain KCOM2805 and almost complete type VI secretion systems in strains KCOM2798 and ATCC49417, which is a new discovery as previous studies did not find the proteins involved in secretion systems IV and VI. Conservation of some virulence factors between different strains was observed, regardless of their genetic diversity and origin. In addition, we performed for the first time a reconstruction analysis of the gene regulatory network, identifying transcription factors and proteins involved in the regulatory mechanisms of bacterial pathogenesis. In particular, QseB regulates the expression of hemagglutinin and arginine deaminase, while Rex may suppress the release of gingipain through interactions with PorV and the formatum/nitrate transporter. Our study highlights the central role of conserved virulence factors and regulatory pathways, particularly QseB and Rex, in P. gingivalis and provides insights into potential therapeutic targets.

Chordoma cancer stem cell subpopulation characterization may guide targeted immunotherapy approaches to reduce disease recurrence.

Introduction: Cancer stem cells (CSCs), a group of tumor-initiating and tumor-maintaining cells, may be major players in the treatment resistance and recurrence distinctive of chordoma. Characterizing CSCs is crucial to better targeting this subpopulation. Methods: Using flow cytometry, six chordoma cell lines were evaluated for CSC composition. In vitro, cell lines were stained for B7H6, HER2, MICA-B, ULBP1, EGFR, and PD-L1 surface markers. Eighteen resected chordomas were stained using a multispectral immunofluorescence (mIF) antibody panel to identify CSCs in vivo. HALO software was used for quantitative CSC density and spatial analysis. Results: In vitro, chordoma CSCs express more B7H6, MICA-B, and ULBP1, assessed by percent positivity and mean fluorescence intensity (MFI), as compared to non-CSCs in all cell lines. PD- L1 percent positivity is increased by >20% in CSCs compared to non-CSCs in all cell lines except CH22. In vivo, CSCs comprise 1.39% of chordoma cells and most are PD-L1+ (75.18%). A spatial analysis suggests that chordoma CSCs cluster at an average distance of 71.51 mm (SD 73.40 mm) from stroma. Discussion: To our knowledge, this study is the first to identify individual chordoma CSCs and describe their surface phenotypes using in vitro and in vivo methods. PD-L1 is overexpressed on CSCs in chordoma human cell lines and operative tumor samples. Similarly, potential immunotherapeutic targets on CSCs, including B7H6, MICA-B, ULBP1, EGFR, and HER2 are overexpressed across cell lines. Targeting these markers may have a preferential role in combating CSCs, an aggressive subpopulation likely consequential to chordoma's high recurrence rate.

Evaluación del conocimiento sobre efecto del cigarrillo en internas fumadoras. Pereira 2004 / Evaluation of Inpatient Smokers’ Knowledge of the Effect of Cigarettes. Pereira 2004

El objetivo general de este estudio fue evaluar el nivel de conocimiento sobre los daños causados por el cigarrillo, en las internas que fuman en un Establecimiento Penitenciario y Carcelario de Mujeres de Pereira, durante el segundo semestre de 2004. Inicialmente se identificaron y cuantificaron las condenadas fumadoras, obteniendo como población estudio un total de 34 internas entre las 149 presentes en la institución. Luego se aplicó una encuesta semiestructurada, la cual permitió recolectar las variables: continuas (nombre, edad etc.) y discontinuas, divididas en variables dicotómicas (procedencia, ¿tiene hijos?) y discretas (escolaridad, cambios en el organismo desde que comenzó a fumar). La información recolectada se condensó en una base de datos en epiinfo, la cual se analizó en forma univariada; posteriormente se realizó análisis bivariado, entre las variables más representativas. Las principales limitaciones en el desarrollo del trabajo fueron la falta de cooperación de las internas, algunas de las cuales presentaron una actitud apática y desconfiada alterando los datos de la encuesta y ocasionando de esta manera sesgos de información, además del horario para la recolección de información, ya que se cruzaba con otras actividades realizadas por ellas o por los estudiantes. El 91 por cien de las internas conoce que el hábito del cigarrillo trae efectos adversos para la salud; de ese 91 por cien, 52 por cien cree que causa cáncer de pulmón; el 15 por cien que causa ‘enfermedad en los pulmones’. El análisis bivariado mostró que a mayor edad, mayor es el conocimiento acerca de los efectos que el cigarrillo ejerce sobre la salud y la relación con el número de cigarrillos consumidos diariamente. Las internas tienen algún conocimiento de los efectos adversos del cigarrillo, porque la mayoría aceptó la relación de éste con enfermedades; pero la concordancia es básicamente para problemas respiratorios, más no para alteraciones sistémicas; además creen que to...