Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy.

The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8 <sup>+</sup> T cells, are important parameters for the control of tumor growth and response to immunotherapy. Here, we show in murine and human cancers that these parameters exhibit circadian oscillations, driven by both the endogenous circadian clock of leukocytes and rhythmic leukocyte infiltration, which depends on the circadian clock of endothelial cells in the tumor microenvironment. To harness these rhythms therapeutically, we demonstrate that efficacy of chimeric antigen receptor T cell therapy and immune checkpoint blockade can be improved by adjusting the time of treatment during the day. Furthermore, time-of-day-dependent T cell signatures in murine tumor models predict overall survival in patients with melanoma and correlate with response to anti-PD-1 therapy. Our data demonstrate the functional significance of circadian dynamics in the tumor microenvironment and suggest the importance of leveraging these features for improving future clinical trial design and patient care

The use of induced pluripotent stem cells in drug development.

Induced pluripotent stem cell (iPSC) technology is revolutionizing medical science, allowing the exploration of disease mechanisms and novel therapeutic molecular targets, and offering opportunities for drug discovery and proof-of-concept studies in drug development. This review focuses on the recent advancements in iPSC technology including disease modeling and control setting in its analytical paradigm. We describe how iPSC technology is integrated into existing paradigms of drug development and discuss the potential of iPSC technology in personalized medicine

Articulation effects in melody recognition memory

10.1080/17470218.2013.766758Quarterly Journal of Experimental Psychology6691774-179