CCL2-expressing astrocytes mediate the extravasation of T lymphocytes in the brain. Evidence from patients with glioma and experimental models in vivo.

CCL2 is a chemokine involved in brain inflammation, but the way in which it contributes to the entrance of lymphocytes in the parenchyma is unclear. Imaging of the cell type responsible for this task and details on how the process takes place in vivo remain elusive. Herein, we analyze the cell type that overexpresses CCL2 in multiple scenarios of T-cell infiltration in the brain and in three different species. We observe that CCL2+ astrocytes play a part in the infiltration of T-cells in the brain and our analysis shows that the contact of T-cells with perivascular astrocytes occurs, suggesting that may be an important event for lymphocyte extravasation.

Radiocirugía con acelerador lineal en el tratamiento del schwannoma vestibular / Linear accelerator radiosurgery for the treatment of vestibular schwannoma

Introducción y objetivo. Entre las opciones terapéuticas para pacientes con schwannoma vestibular se encuentra la radiocirugía. Presentamos así nuestra experiencia en el tratamiento de esta patología con esta técnica. Pacientes y métodos. Estudio retrospectivo de 20 pacientes (11 mujeres y 9 varones; edad media: 55,15 años) con diagnóstico de schwannoma vestibular, que recibieron tratamiento con radiocirugía con acelerador lineal desde abril del 2005 hasta diciembre del 2008. El tiempo de seguimiento fue de 12-42 meses, tanto clínico, con valoración de los pares craneales VII (escala de House-Brackmann) y VIII (escala de Gardner-Robertson), como radiológico (con medición del volumen tumoral). Se emplearon el test exacto de Fisher y la prueba de regresión logística para el análisis estadístico. Resultados. El 25% presentó algún empeoramiento de la audición. Cinco pacientes presentaron tumores grandes en el momento del tratamiento (iguales o mayores que 3,5 cm3), de los cuales cuatro empeoraron de cefalea, inestabilidad, mareos/vértigo, parestesias faciales y acúfenos, con una asociación estadísticamente significativa (p < 0,05) en las pruebas aplicadas. A partir del primer año del tratamiento, se observó una tendencia a la disminución del volumen tumoral, sin observarse ningún crecimiento de la lesión a medio-largo plazo, con control local del 100%. Conclusiones. La radiocirugía se ofrece como una alternativa de tratamiento para pacientes con schwannoma vestibular de tamaño adecuado, con alta seguridad terapéutica, que emplea dosis relativamente bajas de radiación, índice bajo de complicaciones y buen control del crecimiento tumoral a medio plazo (AU)

Introduction and aim. Radiosurgery is among the treatment options for patients with vestibular schwannoma. We present the experience in our institution in the treatment of this disease with this technique. Patients and methods. A retrospective study was made including 20 patients (11 women and 9 men; median age: 55.15 years-old) with vestibular schwannoma who received linear accelerator radiosurgery treatment since April 2005 until December 2008. Follow-up period was between 12 and 42 months, considering clinical examination of cranial nerves VII (House-Brackmann scale) and VIII (Gardner-Robertson scale) as well as radiological findings (considering tumor volume). For statistical analysis, the Fisher’s exact test and logistic regression test were used. Results. Certain worsening of hearing function was present in 25% of the patients. Five patients had large tumors at the moment of the treatment (equal or larger than 3.5 cm3), from which four deteriorated from headache, unsteady gait, dizziness/vertigo, facial numbness and tinnitus, with statistical significance (p < 0.05). From the first year of treatment on, there was a tumor volume decrease tendency, with no tumor growth in the medium/long term follow-up, achieving a local control rate of 100%. Conclusions. Radiosurgery has become an alternative in the treatment of patients with vestibular schwannoma of appropriate size, with high safety level, using low radiation doses, low rate of complications and good tumor control rate in the medium term follow-up (AU)

Infiltrating CTLs in human glioblastoma establish immunological synapses with tumorigenic cells.

The immunological synapse between T cells and tumor cells is believed to be important for effective tumor clearance. However, the immunological synapse has never been imaged or analyzed in detail in human tissue. In this work, intercellular interactions between T cells and tumor cells were analyzed in detail in human glioblastoma. After characterization of the population of infiltrating T cells by multiple immunofluorescence staining and stereological quantification, the microanatomy of T cell-tumor cell intercellular communication was analyzed in detail using confocal microscopy and three-dimensional rendering. Cytotoxic T lymphocytes that infiltrated human glioblastoma underwent rearrangement when in contact with tumor cells, to form a three-dimensional structure in the intercellular contact area; this was characterized by microclusters of the CD3/TCR complex, re-arrangement of the cytoskeleton, and granzyme B polarization. In addition, such T cell-targeted cells show fragmentation of the microtubular system and increased expression levels of cleaved caspase 3, which suggests that cytotoxic T lymphocytes likely provoke changes in tumor cells and subsequently induce cell death. These results show that the formation of the cytotoxic T lymphocyte immunological synapse occurs in human tissue and may be relevant for the effective immune-mediated clearance of tumorigenic cells, therefore opening up new avenues for glioblastoma immunotherapy.