The two T cell inhibitory receptors PD-1 and TIM-3 are co-expressed during exhausted T cell differentiation, and recent evidence suggests that their crosstalk regulates T cell exhaustion and immunotherapy efficacy; however, the molecular mechanism is unclear. Here we show that PD-1 contributes to the persistence of PD-1+TIM-3+ T cells by binding to the TIM-3 ligand galectin-9 (Gal-9) and attenuates Gal-9/TIM-3-induced cell death. Anti-Gal-9 therapy selectively expands intratumoral TIM-3+ cytotoxic CD8 T cells and immunosuppressive regulatory T cells (Treg cells). The combination of anti-Gal-9 and an agonistic antibody to the co-stimulatory receptor GITR (glucocorticoid-induced tumor necrosis factor receptor-related protein) that depletes Treg cells induces synergistic antitumor activity. Gal-9 expression and secretion are promoted by interferon β and γ, and high Gal-9 expression correlates with poor prognosis in multiple human cancers. Our work uncovers a function for PD-1 in exhausted T cell survival and suggests Gal-9 as a promising target for immunotherapy.

performed experiments and analyzed data. Qinghai Ye provided patient tissue samples. Qiongzhu Dong, Hirohito Yamaguchi, and Yi Du provided scientific input and critical cells. Jennifer L. Hsu revised the manuscript. Mien-Chie Hung supervised the entire project, designed the experiments, analyzed data, and wrote the manuscript.

Coronavirus disease 2019 (COVID-19) pandemic may exert adverse impacts on sleep among populations, which may raise awareness of the burden of sleep disturbance, and the demand of intervention strategies for different populations. We aimed to summarize the current evidence for the impacts of COVID-19 on sleep in patients with COVID-19, healthcare workers (HWs), and the general population. We searched PubMed and Embase for studies on the prevalence of sleep disturbance. Totally, 86 studies were included in the review, including 16 studies for COVID-19 patients, 34 studies for HWs, and 36 studies for the general population. The prevalence of sleep disturbance was 33.3%–84.7%, and 29.5–40% in hospitalized COVID-19 patients and discharged COVID-19 survivors, respectively. Physiologic and psychological traumatic effects of the infection may interact with environmental factors to increase the risk of sleep disturbance in COVID-19 patients. The prevalence of sleep disturbance was 18.4–84.7% in HWs, and the contributors mainly included high workloads and shift work, occupation-related factors, and psychological factors. The prevalence of sleep disturbance was 17.65–81% in the general population. Physiologic and social-psychological factors contributed to sleep disturbance of the general population during COVID-19 pandemic. In summary, the sleep disturbance was highly prevalent during COVID-19 pandemic. Specific health strategies should be implemented to tackle sleep disturbance.

The gene encoding STAT3, which is located on chromosome 12, consists of 750 to 850 amino acids and has a molecular weight of 84-113 kDa. STAT3 can be activated in three ways, namely, via the JAK-Stat way, Ras-MAPK approach, and size-independent enzymatic activation. Among them, the classic one is the Stat3 JAK-Stat way of signaling and transcription. In a number of cytokines and growth factor stimulators, STAT3 activates tyrosine or serine kinase