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

Yellowfin tuna behavioural ecology and catchability in the South Atlantic: The right place at the right time (and depth).

The yellowfin tuna (Thunnus albacares: YFT) is a widely distributed, migratory species that supports valuable commercial fisheries. Landings of YFT are seasonally and spatially variable, reflecting changes in their availability and accessibility to different fleets and metiers which, in turn, has implications for sustainable management. Understanding the dynamics of YFT behaviour and how it is affected by biological and ecological factors is therefore of consequence to fisheries management design. Archival and pop-up satellite tags (PSAT) were used in the South Atlantic Ocean around St Helena between 2015 and 2020 to collect information on the movements, foraging and locomotory behaviour of YFT. The study aimed to (1) identify vertical behaviour of YFT within St Helena's EEZ; (2) assess the timing and depth of potential feeding events and (3) to use the information to inform on the catchability of YFT to the local pole and line fishing fleet. Results indicate that the YFT daytime behaviour shifted between shallow with high incidence of fast starts in surface waters in summer months (December to April), to deep with high incidence of strikes at depth in colder months (May to November). Catchability of YFT was significantly reduced between May and November as YFT spent more time at depths below 100 m during the day, which coincides with a reduction in the quantity of YFT caught by the inshore fleet

CuTCNQ resistive nonvolatile memories with a noble metal bottom electrode

Resistive electrical switching of the organic semiconductor Cu-tetracyanoquinodimethane (CuTCNQ) was investigated between gold bottom and aluminum top contacts. Corresponding Au/CuTCNQ/Al crossbar memories achieved several thousand write/erase cycles. The switching process was further studied by current-time measurements, and temperature-dependent measurements of the on state conductivity. (c) 2007 American Institute of Physics.status: publishe

Trial watch: Dendritic cell (DC)-based immunotherapy for cancer

Dendritic cell (DC)-based vaccination for cancer treatment has seen considerable development over recent decades. However, this field is currently in a state of flux toward niche-applications, owing to recent paradigm-shifts in immuno-oncology mobilized by T cell-targeting immunotherapies. DC vaccines are typically generated using autologous (patient-derived) DCs exposed to tumor-associated or -specific antigens (TAAs or TSAs), in the presence of immunostimulatory molecules to induce DC maturation, followed by reinfusion into patients. Accordingly, DC vaccines can induce TAA/TSA-specific CD8(+)/CD4(+) T cell responses. Yet, DC vaccination still shows suboptimal anti-tumor efficacy in the clinic. Extensive efforts are ongoing to improve the immunogenicity and efficacy of DC vaccines, often by employing combinatorial chemo-immunotherapy regimens. In this Trial Watch, we summarize the recent preclinical and clinical developments in this field and discuss the ongoing trends and future perspectives of DC-based immunotherapy for oncological indications

Trial watch: Dendritic cell (DC)-based immunotherapy for cancer

Dendritic cell (DC)-based vaccination for cancer treatment has seen considerable development over recent decades. However, this field is currently in a state of flux toward niche-applications, owing to recent paradigm-shifts in immuno-oncology mobilized by T cell-targeting immunotherapies. DC vaccines are typically generated using autologous (patient-derived) DCs exposed to tumor-associated or -specific antigens (TAAs or TSAs), in the presence of immunostimulatory molecules to induce DC maturation, followed by reinfusion into patients. Accordingly, DC vaccines can induce TAA/TSA-specific CD8(+)/CD4(+) T cell responses. Yet, DC vaccination still shows suboptimal anti-tumor efficacy in the clinic. Extensive efforts are ongoing to improve the immunogenicity and efficacy of DC vaccines, often by employing combinatorial chemo-immunotherapy regimens. In this Trial Watch, we summarize the recent preclinical and clinical developments in this field and discuss the ongoing trends and future perspectives of DC-based immunotherapy for oncological indications

Obesity-associated changes in molecular biology of primary breast cancer

Abstract: Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients' body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring