MERTK (MER Proto-Oncogene, Tyrosine Kinase)

CPL423 showed high permeability, metabolic stability, and low cardiovascular liability. CPL423 provides direct antitumor activity via dual TAM/FLT3 inhibition and immune-mediated effects on antigen-presenting cells, addressing resistance mechanisms in AML and TAM/AXL-driven solid tumors and supporting further development, including combination regimens.

We are studying the crucial role of new technologies, particularly multi-omic spatial models and high-precision organoids, in fostering mechanistic discoveries. These discoveries pave the way for new macrophage-focused therapeutic strategies, including the precise stratification of patients using biomarkers from liquid biopsies (such as soluble SPP1 and MARCO) and the development of targeted drug delivery systems for the selective modulation of macrophage function, thus establishing a new paradigm for therapeutic interventions in pulmonary fibrosis with concomitant lung cancer.

This study shows that UNC569 potently suppresses PDAC cell proliferation and clonogenic growth, inhibits migration and invasion by attenuating epithelial-mesenchymal transition, and enhances the sensitivity of PDAC cells to Gemcitabine while promoting apoptosis. Mechanistically, UNC569 induces DNA damage-mediated G2/M phase arrest and activates JNK/p38 mitogen-activated protein kinase-dependent apoptotic signaling. Collectively, these results establish MerTK as a promising therapeutic target in PDAC and highlight the translational potential of UNC569 as a dual-pathway inhibitor for PDAC treatment.

Our study reveals a myeloid-centered regulatory network in thyroid cancer and highlights TNFSF12 as a context-dependent oncogene, offering novel insights into targeted therapy and immunotherapeutic strategies.

In turn, the Arg-1+ M-MDSCs count in patients receiving non-steroidal anti-inflammatory drugs and having higher disease activity was reduced, while in the patient group receiving tumor necrosis factor alpha-inhibitors and having lower activity, it was increased. The obtained results may indicate a positive role of PD-1 in preventing inflammation in axSpA, whereas Tim-3 presumably weakens the anti-inflammatory M-MDSC potential in axSpA.

Our study systematically revealed the evidence establishing GAS6 as an oncogenic driver and a regulator of the immunosuppressive microenvironment across human cancers. These findings furnish a mechanistic rationale for therapeutically targeting the GAS6/TAM axis to subvert immune tolerance and potentiate chemoradiation.

Herein, we develop an MRX-2843 (MerTK inhibitor) and Mn2+ codelivered defective metal-organic framework (copper-2,3,6,7,10,11-hexaiminotriphenylene (Cu-HITP))-based single-site nanozyme (Ir@D-Cu-HITP-MMP) for antitumor immunotherapy via innate immune-checkpoint blockade...This synergizes with Mn2+ to enhance the stimulator of interferon genes (STING) activation, triggering robust immune responses. Overall, Ir@D-Cu-HITP-MMP demonstrates potent antitumor effects by activating powerful innate and adaptive immune responses.

Furthermore, elevated dopamine and motor learning differentially regulated postsynaptic elimination in MSNs depending on dopamine receptor subtype, leading to MEGF10-dependent changes in synaptic remodeling and quantal properties. These findings identify astrocytic MEGF10 as a key mediator of dopamine- and activity-dependent synapse remodeling in the striatum.

These findings suggest a potential autophagy-mediated regulatory mechanism in RA macrophage function.Abbreviations: ATG: autophagy related; BECN1: beclin 1; IL: interleukin; LAMP1: lysosomal associated membrane protein 1; LIS: less-inflammatory synovium; MAP1LC3/LC3: microtubule sssociated protein 1 light chain 3; MFI: mean fluorescence intensity; OA: osteoarthritis; PG: phagophore; RA: rheumatoid arthritis. SQSTM1: sequestosome 1; TNF: tumor necrosis factor; WIPI2: WD repeat domain, phosphoinositide interacting 2.

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.