Genome-wide CRISPR screening identifies tyrosylprotein sulfotransferase-2 as a target for augmenting anti-PD1 efficacy.

BACKGROUND: Immune checkpoint therapy (ICT) provides durable responses in select cancer patients, yet resistance remains a significant challenge, prompting the exploration of underlying molecular mechanisms. Tyrosylprotein sulfotransferase-2 (TPST2), known for its role in protein tyrosine O-sulfation, has been suggested to modulate the extracellular protein-protein interactions, but its specific role in cancer immunity remains largely unexplored. METHODS: To explore tumor cell-intrinsic factors influencing anti-PD1 responsiveness, we conducted a pooled loss-of-function genetic screen in humanized mice engrafted with human immune cells. The responsiveness of cancer cells to interferon-γ (IFNγ) was estimated by evaluating IFNγ-mediated induction of target genes, STAT1 phosphorylation, HLA expression, and cell growth suppression. The sulfotyrosine-modified target gene of TPST2 was identified by co-immunoprecipitation and mass spectrometry. The in vivo effects of TPST2 inhibition were evaluated using mouse syngeneic tumor models and corroborated by bulk and single-cell RNA sequencing analyses. RESULTS: Through in vivo genome-wide CRISPR screening, TPST2 loss-of-function emerged as a potential enhancer of anti-PD1 treatment efficacy. TPST2 suppressed IFNγ signaling by sulfating IFNγ receptor 1 at Y397 residue, while its downregulation boosted IFNγ-mediated signaling and antigen presentation. Depletion of TPST2 in cancer cells augmented anti-PD1 antibody efficacy in syngeneic mouse tumor models by enhancing tumor-infiltrating lymphocytes. RNA sequencing data revealed TPST2's inverse correlation with antigen presentation, and increased TPST2 expression is associated with poor prognosis and altered cancer immunity across cancer types. CONCLUSIONS: We propose TPST2's novel role as a suppressor of cancer immunity and advocate for its consideration as a therapeutic target in ICT-based treatments.

Exploration of Risk Factors for Falls Using Electronic Nursing Records.

INTRODUCTION: The purpose was to identify fall risk factors between admission day and fall occurred day using electronic nursing records and the Morse Fall Scale (MFS). METHODS: The MFS and fall related data were obtained through retrospective chart review from June 1, 2014 to May 31, 2015. Descriptive statistics and McNemar test were used for statistical tests. RESULTS: Fall was evaluated in 447 events, 16 patients experienced recurrent fall. Pain, emotional distress, urinary problems and fever were significant differences between admission day and fall occurred day. There were explored significant MFS risk factors in risk group, history of falling, second diagnosis, IV catheter status, medication concerning fall risk, mental status, general weakness and gait in MFS subscales. DISCUSSION: Routine fall screening is important for early detection of fall. Identification of high-risk group and using fall prevention guidelines could improve prevention of fall.

Evaluation of Nursing Actions Documented in EHRs for Patients Falls Against Clinical Practice Guidelines in a Korean Tertiary Hospital.

PURPOSE: Many fall prevention strategies have been used for reducing fall rates. The purpose was to evaluate fall prevention nursing against clinical practice guidelines and effectiveness of preventing strategies according to risk group. METHODS: We developed fall survey form after securing consistencies (Fleiss Kappa = .83). The EHRs of 447 events from June 1, 2014 to May 31, 2015 were reviewed. Descriptive statistics and Chi-square test were used for statistical tests. RESULTS: There were recorded 'Keep bed with brakes locked' in 272 patients (60.9%). Compared with clinical practice guidelines, 'instruction of patients to ask for help actively' and 'keep patients care areas uncluttered.' actions were few in EHRs. There were significant differences between risk groups in 28 nursing actions. DISCUSSION: This study shows that fall prevention strategies according to risk groups are insufficient to prevent falls. Instruction about critical time that patients should ask for help should be considered.