MERTK (MER Proto-Oncogene, Tyrosine Kinase)

Targeting LEPR+ KCs enhances tumor immunogenicity and promotes antitumor T cell responses. Together, our study highlights the potential of combining efferocytosis inhibitors with immunotherapy to overcome chemoresistance.

Combining CTX with the next generation MERTK-selective inhibitor UNC2371 (MRX-2843) drives complete remissions in both models, but durable long-term responses occurred selectively in the basal-like subtype model. Suppressive myeloid programing limits effective adaptive immune engagement in TNBC usually resulting in ICB treatment resistance and tumor recurrence. This study identifies a therapeutically actionable myeloid interferon checkpoint in which MERTK inhibition stabilizes CXCL9⁺ monocyte-macrophage programming to promote CD4⁺ T cell dependent immune memory and durable tumor control in basal-like TNBC.

Notably, over 80% of genes upregulated in ZFTA-RELAfus tumors were downregulated following MERTK inhibition, indicating a strong dependency on this pathway for tumor maintenance. These findings define a signaling vulnerability in ZFTA-RELA-driven ependymomas and support the clinical development of MERTK-targeted therapies for patients with the high-risk EPN-E1 subtype.

Furthermore, unlike other MERTK-targeting small molecules or antibodies, no retinal toxicity of RGX-019-MMAE was observed in vivo. These findings reveal that combined therapeutic targeting of MERTK in cancer cells and M2 macrophages offers enhanced opportunities for anti-tumor efficacy in a wide range of MERTK-expressing tumors.

Additionally, omentin-1 facilitated the polarization of macrophages toward the M2 phenotype and attenuated the inflammatory responses induced by lipopolysaccharide (LPS). The findings of this study indicate that omentin-1 suggests its potential as a candidate for developing novel adjunctive therapies for chronic non-healing diabetic wounds.

We established an efferocytosis-related prognostic signature and elucidated its underlying mechanism wherein MAGEA11 promoted immunosuppression via a Gas6-MERTK/AXL-dependent efferocytosis circuit. This integrated study positions efferocytosis as a key driver of the OS microenvironment and a promising target for clinical intervention.

Furthermore, compound 31l displayed a favorable metabolic stability profile in both human and mouse liver microsome screens and an oral bioavailability of 56%. This finding suggests that lead compound 31l is a promising tool for further optimization and development as a potential MERTK/FLT3 dual inhibitor anti-AML drug candidate.

This study employed multi-parametric flow cytometry and clodronate liposome (CL) depletion to systematically re-evaluate splenic CD11chighMHCIIhigh cDCs in C57BL/6 mice...These findings demonstrate unprecedented cDC plasticity driven by microenvironmental signals, revising conventional classification frameworks and proposing new targets for DC-based immunotherapies in autoimmunity and cancer. Our phenotypic mapping provides a foundational framework for future functional investigations into these novel subsets.

Clinically, elevated serum levels of soluble MerTK (s-Mer) correlated with hepatic injury severity and Caspase-1 activation in patients after partial hepatectomy or liver transplantation. Our findings suggest a potential therapeutic strategy for LIRI prevention and treatment.

Our study delineates regulation of C1q and subsequent monocyte antibacterial functions as a potential mechanism of UTI response regulated by SGLT2i. C1q should also be explored as a possible pathogenic factor in chronic kidney damage amenable to SGLT2i.

Successfully modeled rats were then randomized into three groups: a model control group, an Xuebijing Injection(8 mL·kg~(-1)) group, and a dexamethasone(5 mg·kg~(-1)) group, with 10 rats in each group...qPCR, Western blot, and immunofluorescence showed that Xuebijing Injection could promote the expression of key factors ProS1, MerTK, and Rac1 involved in efferocytosis. Xuebijing Injection significantly alleviates inflammatory infiltration and injury in the lung tissue of ALI rats by enhancing efferocytosis in alveolar macrophages and promoting apoptotic cell clearance to suppress inflammation.

The MLCS is a scoring tool to assist in timing and selecting therapeutic combinations of ARPI with TREM2 or CSF1R blockade, PARPi with STING modulation, and ARPI with anti-CD47 therapy. Integrating mechanistic and translational data provides a foundation for biomarker-guided regimens capable of converting prostate cancer from an immune-cold disease to an immune-responsive state.