Journal: Advanced Science

Article Title: Fc‐Dependent Targeting of the GAS6–MERTK Axis With Monoclonal and Bispecific Antibodies Overcomes Drug Resistance Across EGFR Mutations in Exons 19, 20, and 21

doi: 10.1002/advs.78290

Figure Lengend Snippet: GAS6 supports survival of TKI‐treated cells; blocking it delays resistance to osimertinib in an animal model. (A) Data were taken from a clinical trial, NCT03433469 (EGFR‐positive NSCLC patients). Patients were treated with osimertinib, and the cohort was segregated into Treatment Naïve (TN), Residual Disease (RD), and Progressive Disease (PD). The volcano plot presents delayed early genes that differ between patients with RD (4 samples) and PD (3 samples). MERTK, AXL, GAS6, and EGFR are highlighted in red. The average log2 of the fold change (FC) and the p ‐values are presented in a table. (B) GAS6 knockout (KO) and GAS6‐overexpressing (OX) PC9 cells were generated. Cells (500/well) were seeded in 96‐well plates and grown for 9 days. The cells were then fixed and stained with crystal violet to estimate cell numbers on specific days. *** , p < 0.001; **** , p < 0.0001. (C) The indicated derivatives of PC9 cells (1 × 10 3 , per well) were seeded in 96‐well plates. Next, cells were treated for 72 h with different concentrations of osimertinib. Cell viability was determined using a colorimetric assay. The histogram depicts cell viability under 10 n m osimertinib. (D‐F) PC9 cells (2.5 × 10 6 ) were injected subcutaneously in the flanks of CD1‐nu/nu mice. Once the tumor became palpable, 5–7 mice were randomized into the indicated 4 groups and treated for five weeks with either osimertinib (10 mg/kg) or/and a mAb197 against GAS6 (0.2 mg per injection; twice weekly). Individual tumor volumes (D) average tumor volumes per group, along with the average recorded on day 47 (E), and Kaplan‐Meier survival plots (F) are shown. Survival analysis was performed using Holm–Šídák's multiple comparisons test to assess statistical significance between treatment groups. The adjusted p ‐value for the comparison between osimertinib alone and osimertinib combined with mAb197 is 0.0044. All experiments were repeated at least twice.

Article Snippet: Balb/c mice were immunized with the extracellular domain of MERTK (SinoBiological, Cat: 10298‐H03H; 25 μg per injection).

Techniques: Blocking Assay, Animal Model, Knock-Out, Generated, 96 Well Plates, Staining, Colorimetric Assay, Injection, Analysis, Comparison

Journal: Advanced Science

Article Title: Fc‐Dependent Targeting of the GAS6–MERTK Axis With Monoclonal and Bispecific Antibodies Overcomes Drug Resistance Across EGFR Mutations in Exons 19, 20, and 21

doi: 10.1002/advs.78290

Figure Lengend Snippet: Dual blockade of EGFR and MERTK using antibodies delays tumor relapses, likely due to the ability of EGFR to interact with MERTK within membrane microdomains. (A, B) CD1‐nu/nu mice were subcutaneously implanted with PC9 cells (2.5 × 10 6 ). Once tumors became palpable, animals (5–7 per group) were randomized and treated twice weekly for 4 weeks with the indicated mAbs (200 µg/injection, intraperitoneally), and/or daily with osimertinib (5 mg/kg; orally). Tumor volumes were measured twice weekly. Tumor volumes on day 47 are shown as mean ± SEM. Statistical significance was determined using an unpaired t ‐test; * , p < 0.05. Tumor volumes and animal survival are shown. The grey‐shaded area indicates the treatment period. Data are presented as tumor volume (mean ± SEM; A) and the corresponding Kaplan–Meier survival curves (B). (C and D) PC9 and H1975 cells (3 × 10 3 ) were seeded in 96‐well plates. The next day, cells were treated for 3 days with different concentrations of osimertinib and MRX‐2843 in pairwise combinations. Following fixation, cells were stained with crystal violet to identify viable cells. The synergy scores of the drugs were calculated based on the Bliss reference model, using SynergyFinder. The red color indicates high synergy scores, implying cooperative EGFR‐MERTK interactions. (E) PC9 cells (1 × 10 4 ) were seeded on coverslips and allowed to adhere overnight. The next day, cells were serum starved for 6 h and treated with either EGF (100 ng/mL) or GAS6 (250 ng/mL) in serum‐free medium. Thereafter, the cells were fixed, permeabilized, and then stained with a rabbit anti‐MERTK antibody, as well as with a murine anti‐human EGFR antibody. Subsequently, a proximity ligation assay was performed using anti‐Rabbit Plus and anti‐Mouse Minus. The amplified product of the PLA test was labeled using a red dye, and nuclei were stained with DAPI. Images were obtained using a Zeiss Spinning Disk confocal microscope, and the analysis was performed using ImageJ. MERTK knockout PC9 cells were used as a negative control. Scale bar, 10 µm. All experiments were repeated twice. (F) PC9 cells were seeded on glass coverslips and serum‐starved for 8 h, followed by stimulation for 60 min with either EGF (100 ng/mL) or Gas6 (250 ng/mL). Cells were then fixed and immunostained for EGFR (green) and nuclear DNA (DAPI; blue) and caveolin‐1 (red). Colocalization of EGFR with caveolin‐1 is indicated by white arrows. Scale bar, 5 µm.

Article Snippet: Balb/c mice were immunized with the extracellular domain of MERTK (SinoBiological, Cat: 10298‐H03H; 25 μg per injection).

Techniques: Membrane, Injection, 96 Well Plates, Staining, Proximity Ligation Assay, Amplification, Labeling, Spinning Disk, Confocal, Microscopy, Analysis, Knock-Out, Negative Control, Glass

Journal: Advanced Science

Article Title: Fc‐Dependent Targeting of the GAS6–MERTK Axis With Monoclonal and Bispecific Antibodies Overcomes Drug Resistance Across EGFR Mutations in Exons 19, 20, and 21

doi: 10.1002/advs.78290

Figure Lengend Snippet:

Article Snippet: MERTK , 4319S , Cell Signaling Technology (CST) , AB_10614528.

Techniques: Cell-Signaling

Journal: Nature Communications

Article Title: Bioinspired porous metal-amino acid nanozymes enable multi-pathway treatment of atherosclerosis through anti-oxidation and pro-efferocytosis

doi: 10.1038/s41467-026-75509-4

Figure Lengend Snippet: a Schematic illustration of the pro-efferocytosis property of MMAzyme-S. (Created in BioRender. Huang, H. (2026) https://BioRender.com/7l5dwq4 ). b CLSM images depicting phagocytosis of CD47-overexpressed ACs in proinflammatory-phenotype macrophages pretreated with different samples. FCM results ( c ) and the corresponding quantitative analysis ( d ) of efferocytosis towards CD47-overexpressed ACs by proinflammatory phenotype macrophages pretreated with different samples ( n = 3 independent biological samples). e The quantitative results of the Western blotting of Mertk in macrophages under different treatments ( n = 3 independent biological samples. Samples in different blots were derived from the same experiment. All gels/blots were processed in parallel. f Schematics illustration for the mechanism of promoting cholesterol efflux mediated by MMAzyme-S (created in BioRender. Huang, H. (2026) https://BioRender.com/o3x56t5 ). g Optical microscopy images of induced foamy cell formation in macrophages under different treatments. h Cholesterol content in the supernatant of foamy cells under different treatments ( n = 4 independent biological samples). i Western blotting analysis of Mertk, PPARγ, LXRα, ABCA1, and ABCG1 in macrophages under different treatments. Corresponding quantitative results of the Western blotting of PPARγ ( j ), LXRα ( k ), ABCA1 ( l ), and ABCG1 ( m ) in macrophages under different treatments ( n = 3 independent biological samples. Samples in different blots were derived from the same experiment. All gels/blots were processed in parallel). Data in ( d , e , h , j – m ) were expressed as mean ± S.D. Significance in ( d , e , h , j – m ) was calculated using one-way ANOVA followed by Tukey’s post hoc test for multiple comparisons. Although the individual values of Group ii and Group iii in ( l ) do not overlap, the statistical analysis does not indicate a significant difference, possibly due to the limited sample size. Source data are provided as a file.

Article Snippet: The following primary antibodies were used in this study: CD47 Rabbit pAb (A1838, ABclonal,1:750), CD36/SR-B3 Rabbit pAb (A5792, ABclonal,1:2500), CCR2 Rabbit pAb (A2855, ABclonal,1:750), Na-K-ATP Rabbit pAb (GB11400, Servicebio,1:2000), MERTK Rabbit pAb (A5443, ABclonal,1:750), LXRα Rabbit mAb (A3974, ABclonal,1:3000), ABCG1 Rabbit mAb (A17907, ABclonal,1:1500), PPARγ Rabbit pAb (WL01800, Wanleibio,1:1000), Anti-ABCA1 antibody ( AB307536 , Abcam,1:1000), GAPDH Rabbit pAb (AC001, ABclonal,1:20000), p-SHP1 (8849, Cell Signaling Technology, 1:1000), HRP-conjugated Goat anti-Rabbit IgG (H+L) (AS014, ABclonal,1:5000).

Techniques: Western Blot, Derivative Assay, Microscopy

Journal: Scientific Reports

Article Title: Glucocorticoids induce a phagocytic C1Q+ macrophage phenotype primed for IFNγ-dependent CXCL9 secretion

doi: 10.1038/s41598-026-52733-y

Figure Lengend Snippet: GC-induced MΦ are highly efficient in C1q-mediated phagocytosis. ( A ) Gene set enrichment analysis (GSEA) of DEGs in MΦ exposed to CM of steroidogenic NCI-H295R cells in comparison to controls. ( B ) Visualization of the enrichment results on phagocytosis ( p < 2.2e-16; FDR: 0.011718). ( C ) Representative flow cytometry plots and ( D ) quantification of phagocytosis by MΦ exposed to CM of steroidogenic NCI-H295R cells or control. CD64 + CFSE+ double-positive cells were considered phagocytic macrophages. Groups were compared using one-way ANOVA with Tukey’s multiple comparisons test. N = 4 biological replicates from independent healthy blood donors ( E ) Percentages of phagocytic MΦ exposed to dexamethasone (100 nM) or control. N = 3 biological replicates from independent healthy blood donors are shown in mean +/- SD. Differences were compared using unpaired t-test. ( F ) Phagocytosis of M1-polarized MΦ after exposure to 10 µg/ml or 20 µg/ml purified human C1q. N = 3 biological replicates from independent healthy blood donors are shown in mean +/- SD. Groups were compared using one-way ANOVA with Tukey’s multiple comparisons test. ( G ) Phagocytosis of dexamethasone (100 nM) -polarized MΦ after exposure to 1 µg/ml, 10 µg/ml or 50 µg/ml anti-C1QA antibody. N = 3 biological replicates from independent healthy blood donors are shown in mean +/- SD. Groups were compared using one-way ANOVA with Tukey’s multiple comparisons test. ( H ) Phagocytosis of dexamethasone (100 nM)-polarized MΦ after exposure to the MerTK inhibitor UNC1062 (100 nM), anti-Gas6 antibody (20 µg/ml) or goat control IgG (20 µg/ml). N = 3 biological replicates from independent healthy blood donors are shown in mean +/- SD. Groups were compared using one-way ANOVA with Tukey’s multiple comparisons test. ( I ) Kaplan-Meier plots of PFS and OS according to tumoral CSF1 and C1QA expression. Higher gene expression was significantly associated with favorable PFS and OS. RNA expression and survival data was extracted from the TCGA dataset ( n = 76). NCI-R = NCI-H295R; mety=metyrapone.

Article Snippet: For inhibition studies, MФ were pre-incubated with the selective MerTK inhibitor UNC1062 (100 nM; MCE: Cat# HY-117548), anti-Gas6 antibody (20 μg/ml; R&D Systems, Cat# AB885, RRID: AB_354376), a goat isotype IgG control (20 μg/ml; Thermo Fisher Scientific, Cat# 02–6202, RRID: AB_2532946), purified C1q (Merck; Cat# C1740) or anti-C1QA antibody (LS-Bio; Cat# LS‐C100911; RRID: AB_2067267) for 30 min before they were added to early ferroptotic tumor cells.

Techniques: Comparison, Flow Cytometry, Control, Purification, Expressing, Gene Expression, RNA Expression