‘Nur'turing tumor T cell tolerance and exhaustion: novel function for Nuclear Receptor Nur77 in immunity

The nuclear receptor Nur77 is expressed in a multitude of tissues, regulating cell differentiation and homeostasis. Dysregulation of Nur77 signaling is associated with cancer, cardiovascular disease, and disorders of the CNS. The role of Nur77 in T cells has been studied for almost 30 years now. There is a clear appreciation that Nur77 is crucial for apoptosis of self-reactive T cells. However, the regulation and function of Nur77 in mature T cells remains largely unclear. In an exciting development, Nur77 has been recently demonstrated to impinge on cancer immunotherapy involving chimeric antigen receptor (CAR) T cells and tumor infiltrating lymphocytes (TILs). These studies indicated that Nur77 deficiency reduced T cell tolerance and exhaustion, thus raising the effectiveness of immune therapy in mice. Based on these novel insights, it may be proposed that regulation of Nur77 activity holds promise for innovative drug development in the field of cellular immunotherapy in cancer. In this review, we therefore summarize the role of Nur77 in T cell selection and maturation; and further develop the idea of targeting its activity in these cells as a potential strategy to augment current cancer immunotherapy treatments.     

Facial emotion recognition in adolescents with personality pathology

It has been argued that a heightened emotional sensitivity interferes with the cognitive processing of facial emotion recognition and may explain the intensified emotional reactions to external emotional stimuli of adults with personality pathology, such as borderline personality disorder (BPD). This study examines if and how deviations in facial emotion recognition also occur in adolescents with personality pathology. Forty-two adolescents with personality pathology, 111 healthy adolescents and 28 psychiatric adolescents without personality pathology completed the Emotion Recognition Task, measuring their accuracy and sensitivity in recognizing positive and negative emotion expressions presented in several, morphed, expression intensities. Adolescents with personality pathology showed an enhanced recognition accuracy of facial emotion expressions compared to healthy adolescents and clients with various Axis-I psychiatric diagnoses. They were also more sensitive to less intensive expressions of emotions than clients with various Axis-I psychiatric diagnoses, but not more than healthy adolescents. As has been shown in research on adults with BPD, adolescents with personality pathology show enhanced facial emotion recognition.     

Novel Approach to Repeated Arterial Blood Sampling in Small Animal PET: Application in a Test-Retest Study with the Adenosine A1 Receptor Ligand [<Superscript>11</Superscript>C]MPDX

Purpose

Small animal positron emission tomography (PET) can be used to detect small changes in neuroreceptor availability. This often requires rapid arterial blood sampling. However, current catheterization procedures do not allow repeated blood sampling. We have developed a procedure which allows arterial sampling on repeated occasions in the same animal.

Procedures

Eleven male Wistar rats were two times catheterized via a superficial branch of a femoral artery and scanned with [¹¹C]MPDX and blood sampling. PET images were co-registered to a magnetic resonance imaging (MRI) template. Regional tracer distribution volumes (V _T) in the brain were calculated by the Logan analysis. The procedure was repeated after 1 week.

Results

Surgery was successful in 90 % of the cases, and discomfort was minor. The V _T data showed small differences between test and retest, low between subject variability, and a strong agreement between and within subjects.

Conclusion

Repeated quantitative imaging with a high reproducibility is possible with this approach.