Cytokinesis is the final step of the cell-division cycle. In fungi, it relies on the coordination of constriction of an actomyosin contractile ring and construction of the septum at the division site. Glucan synthases synthesize glucans, which are the major components in fungal cell walls and division septa. It is known that Rho1 and Rho2 GTPases regulate glucan synthases Bgs1, Bgs4, and Ags1, and Sbg1 and the F-BAR protein Cdc15 play roles in Bgs1 stability and delivery to the plasma membrane. Here we characterize Smi1, an intrinsically disordered protein that interacts with Bgs4 and regulates its trafficking and localization in fission yeast. Smi1 is important for septum integrity, and its absence causes severe lysis during cytokinesis. Smi1 localizes to secretory vesicles and moves together with Bgs4 towards the division site. The concentrations of the glucan synthases Bgs1 and Bgs4 and the glucanases Agn1 and Bgl2 decrease at the division site in smi1 mutant, but Smi1 seems to be more specific to Bgs4. Mistargeting of Smi1 to mitochondria mislocalizes Bgs4, but not Bgs1. Together, our data reveal a novel regulator of glucan synthases and glucanases, Smi1, which is more important for Bgs4 trafficking, stability, and localization during cytokinesis. [Media: see text] [Media: see text]

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9067 Background: To date, few studies have associated elevated Absolute Eosinophil Count (AEC) with improved outcome to a single agent immune checkpoint inhibitor (ICI) as first or subsequent line of therapy in patients with NSCLC. Here, we investigated prognostic utility of AEC and the sex difference in patients undergoing standard-of-care first-line ICI with or without chemotherapy for metastatic NSCLC. Methods: This was a retrospective cohort study of 310 patients with Stage IV NSCLC treated with first-line ICI-based therapies (alone or in combination with chemotherapy) under IRB approved protocol 2021C0069. Demographic data are summarized in the table. Peripheral AEC measured by cells/microL was collected within 1 week before the start of therapy. Eosinophil count was evaluated in males and females by both descriptive statistics and Chi-squared test as a continuous and categorical variable, respectively. High level of baseline AEC was defined as 75th percentile (270 cells/microL). Overall Survival (OS) was plotted using the Kaplan-Meier method and p-values from log-rank test were reported. PD‐L1 was assessed by tumor proportion score (TPS) and classified into < 1%, 1 to 49% and ≥ 50%. Results: 14% male vs 6% female patients were found to have peripheral eosinophilia (AEC ≥ 500) at the start of immunotherapy, p = 0.02. Patients with lower AEC had a median OS of 18.6 months vs 29.3 months in those with higher AEC ( p = 0.02, HR: 1.465, 95% Cl: 1.073-2.001). Patients with higher baseline AEC showed a sex difference, with median OS of 23.9 months in males vs NR median OS in females with over 60% survival at the time of last follow up ( p = 0.04, HR: 1.934, 95% Cl: 1.040-3.597). This difference was seen with ICI monotherapy ( p = 0.02, HR: 2.630, 95% Cl: 1.192-5.805), but not ICI with chemotherapy ( p = 0.83, HR: 1.116, 95% Cl: 0.4054-3.070). Higher AEC was associated with TPS ≥ 50% in both males and females ( p = 0.004 and 0.001, respectively), though no significant sex difference was observed. Conclusions: Our data highlight critical sex differences in interpretation of baseline AEC in patients on ICI therapy for metastatic NSCLC. While males have a higher frequency of peripheral eosinophilia, higher AEC correlates to improved OS predominantly in females. Further, this female-biased outcome is seen only with ICI monotherapy, even though higher AEC is associated with high PD-L1 expression in both sexes. Future studies are indicated to assess the longitudinal trend in eosinophil count as well as their active versus passive role in anti-tumor immunity and toxicity in the presence or absence of chemotherapy. [Table: see text]