Tumor microenvironment of Burkitt lymphoma: different immune signatures with different clinical behavior.

ABSTRACT: Burkitt lymphoma (BL) is characterized by a tumor microenvironment (TME) in which macrophages represent the main component, determining a distinct histological appearance known as "starry sky" pattern. However, in some instances, BL may exhibit a granulomatous reaction that has been previously linked to favorable prognosis and spontaneous regression. The aim of our study was to deeply characterize the immune landscape of 7 cases of Epstein-Barr virus-positive (EBV+) BL with granulomatous reaction compared with 8 cases of EBV+ BL and 8 EBV-negative (EBV-) BL, both with typical starry sky pattern, by Gene expression profiling performed on the NanoString nCounter platform. Subsequently, the data were validated using multiplex and combined immunostaining. Based on unsupervised clustering of differentially expressed genes, BL samples formed 3 distinct clusters differentially enriched in BL with a diffuse granulomatous reaction (cluster 1), EBV+ BL with typical starry sky pattern (cluster 2), EBV- BL with typical "starry sky" (cluster 3). We observed variations in the immune response signature among BL with granulomatous reaction and BL with typical "starry sky," both EBV+ and EBV-. The TME signature in BL with diffuse granulomatous reaction showed a proinflammatory response, whereas BLs with "starry sky" were characterized by upregulation of M2 polarization and protumor response. Moreover, the analysis of additional signatures revealed an upregulation of the dark zone signature and epigenetic signature in BL with a typical starry sky. Tumor-associated macrophages and epigenetic regulators may be promising targets for additional therapies for BL lymphoma, opening novel immunotherapeutic strategies.

SOX11 expression is restricted to EBV-negative Burkitt lymphoma and is associated with molecular genetic features.

ABSTRACT: SRY-related HMG-box gene 11 (SOX11) is a transcription factor overexpressed in mantle cell lymphoma (MCL), a subset of Burkitt lymphomas (BL) and precursor lymphoid cell neoplasms but is absent in normal B cells and other B-cell lymphomas. SOX11 has an oncogenic role in MCL but its contribution to BL pathogenesis remains uncertain. Here, we observed that the presence of Epstein-Barr virus (EBV) and SOX11 expression were mutually exclusive in BL. SOX11 expression in EBV-negative (EVB-) BL was associated with an IG∷MYC translocation generated by aberrant class switch recombination, whereas in EBV-negative (EBV-)/SOX11-negative (SOX11-) tumors the IG∷MYC translocation was mediated by mistaken somatic hypermutations. Interestingly, EBV- SOX11-expressing BL showed higher frequency of SMARCA4 and ID3 mutations than EBV-/SOX11- cases. By RNA sequencing, we identified a SOX11-associated gene expression profile, with functional annotations showing partial overlap with the SOX11 transcriptional program of MCL. Contrary to MCL, no differences on cell migration or B-cell receptor signaling were found between SOX11- and SOX11-positive (SOX11+) BL cells. However, SOX11+ BL showed higher adhesion to vascular cell adhesion molecule 1 (VCAM-1) than SOX11- BL cell lines. Here, we demonstrate that EBV- BL comprises 2 subsets of cases based on SOX11 expression. The mutual exclusion of SOX11 and EBV, and the association of SOX11 with a specific genetic landscape suggest a role of SOX11 in the early pathogenesis of BL.

Interferência e características do edema periorbital no exame pupilar após craniotomia / Interference and characteristics of periorbital edema in pupil examination after craniotomy

Objetivo Avaliar a interferência e características do edema periorbital no exame pupilar, em pacientes submetidos a craniotomia por via anterior. Métodos Estudo de coorte prospectivo realizado em pacientes no pós-operatório na unidade de terapia intensiva e internação de neurocirurgia. A interferência e características do edema periorbital no exame pupilar foram avaliados da admissão do paciente até sétimo dia de pós-operatório. O exame pupilar foi realizado por enfermeiros. Resultados Foram avaliados 100 pacientes e a incidência de edema periorbital foi de 80%. O enfermeiro não realizou o exame pupilar em 24 (30%) pacientes. As características que influenciaram na realização do exame pupilar foram coloração arroxeada e intenso edema periorbital. Conclusão O edema periorbital estava presente na maioria dos pacientes no pós-operatório de craniotomia e o exame pupilar não foi realizado em 30% dos pacientes. A presença de intenso edema periorbital e de coloração arroxeada foram características que prejudicaram o exame pupilar...

Objective To assess the interference and the characteristics of periorbital edema in pupil examination with patients who underwent anterior craniotomy. Methods Prospective cohort study conducted postoperatively in an intensive care unit and neurosurgery ward. Interference and characteristics of periorbital edema in pupil examination were assessed between patients’ admission and the seventh day of the postoperative period. Pupil examination was performed by nurses. Results One hundred patients were examined and the incidence of periorbital edema was 80%. Pupil examination was not performed by a nurse in 24 patients (30%). The characteristics that influenced the performance of pupil examination were purplish coloration and severe periorbital edema. Conclusion Periorbital edema was found in most postoperative craniotomy patients and pupil examination was not performed in 30% of them. The presence of severe periorbital edema and purplish coloration were the factors that hampered pupil examination...