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Neuroinflammation is a recognized complication of immunotherapeutic approaches such as immune checkpoint inhibitor treatment, chimeric antigen receptor therapy, and graft versus host disease (GVHD) occurring after allogeneic hematopoietic stem cell transplantation. While T cells and inflammatory cytokines play a role in this process, the precise interplay between the adaptive and innate arms of the immune system that propagates inflammation in the central nervous system remains incompletely understood. Using a murine model of GVHD, we demonstrate that type 2 cannabinoid receptor (CB2R) signaling plays a critical role in the pathophysiology of neuroinflammation. In these studies, we identify that CB2R expression on microglial cells induces an activated inflammatory phenotype that potentiates the accumulation of donor-derived proinflammatory T cells, regulates chemokine gene regulatory networks, and promotes neuronal cell death. Pharmacological targeting of this receptor with a brain penetrant CB2R inverse agonist/antagonist selectively reduces neuroinflammation without deleteriously affecting systemic GVHD severity. Thus, these findings delineate a therapeutically targetable neuroinflammatory pathway and have implications for the attenuation of neurotoxicity after GVHD and potentially other T cell-based immunotherapeutic approaches., Introduction Neurological inflammation and cognitive dysfunction are increasingly recognized complications of cancer immunotherapeutic approaches such as immune checkpoint inhibitor treatment (1, 2), chimeric antigen receptor therapy (3, 4), and graft [...]

Abstract Background Changing epidemiology and diagnostic difficulties of paediatric tuberculosis (TB) are being increasingly reported. Our aim was to describe clinico-epidemiological profile and diagnostic procedures used for paediatric TB. Methods A retrospective case-series analysis was carried out in a tertiary care teaching hospital of western Nepal. All pediatric TB (age 0-14 years) patients registered in DOTS clinic during the time period from March, 2003 to July, 2008 were included. Medical case files were reviewed for information on demography, clinical findings, investigations and final diagnosis. Analysis was done on SPSS package. Results were expressed as rates and proportions. Chi square test was used to test for statistical significance. Results About 17.2% (162/941) of TB patients were children. Common symptoms were cough, fever and lymph node swelling. The types of TB were pulmonary TB (46.3%, 75/162), followed by extra-pulmonary TB (41.4%, 67/162). Twelve patients (7.4%) had disseminated TB. Distribution of types of TB according to gender was similar. PTB was common in younger age than EPTB which was statistically significant. EPTB was mainly localized to lymph node (38, 50.7%), and abdomen (9, 12%). Five main investigations namely Mantoux test, BCG test, chest radiograph, erythrocyte sedimentation rate (ESR) and fine needle aspiration cytology (FNAC) or biopsy were carried out to diagnose TB. Conclusions Paediatric TB in both pulmonary and extrapulmonary forms is a common occurrence in our setting. Age incidence according to type of TB was significant. Diagnosis was based on a combination of epidemiological and clinical suspicion supported by results of various investigations.