ADGRG1 (Adhesion G Protein-Coupled Receptor G1)

This study provides the first high-content proteomic atlas of intrathecal ICI therapy in LM, identifies intrathecal ICI therapy-specific immune remodeling in LM, and establishes a CSF-based predictive model with high accuracy. ADGRG1 represents a promising biomarker of treatment responsiveness and a potential mechanistic link between macrophage biology and LM progression.

We further demonstrate that cancer-cell-derived migrasomes transfer aGPCRs such as GPR56 to endothelial cells in vitro and in vivo, thereby enhancing angiogenic potential. Together, our findings uncover that aGPCRs promote migrasome formation and provide a novel mechanism of cell-cell communications through EV-mediated intercellular spread of active GPCRs.

Mechanistically, we show that ADGRG1 promotes preOL maturation by RhoA activation. Collectively, these findings reveal an ADGRG1-mediated RhoA signaling pathway that governs axon ensheathment and myelin formation.

In conclusion, mega-scale single-cell monitoring of graft and hematopoietic immune cell reconstitution allowed us to demonstrate that MDGA1 and ADGRG1 may function as complementary biomarkers expressed by distinct circulating T cells that are associated with divergent outcomes in AML patients, enabling precise risk stratification of alloHSCT outcomes and presenting potential therapeutic targets.

Comparative transcriptomic analysis revealed distinct gene expression profiles between CD4+GPR56+ and CD4+GPR56- T cells, with enriched pathways related to immune activation and cytotoxicity. Together, our results identify GPR56 as a novel and functionally significant surface marker for CD4+ CTLs, providing new insights into their role in autoimmune disorders and their potential for targeted therapeutic strategies.

We provide a comprehensive overview of the ADC landscape, examining key targets on bulk tumor cells (CEACAM5, HER2), cancer stem cells (LGR5, GPR56), and stromal components. We conclude that the future of ADCs in CRC lies in their rational application as immune-priming agents, creating powerful synergies in combination with checkpoint inhibitors to break therapeutic resistance and durably improve patient outcomes.

In addition, we found that higher levels of DEPs, such as CD27, TNF, CCL3, CCL4, IL12RB1, PDCD1, and GZMB, in patients with genetic alterations associated with poor prognosis. Our Olink proteomics analysis identified nine key proteins that were differentially expressed between the pediatric B-ALL and control groups, which may contribute to the diagnosis and/or risk stratification of pediatric B-ALL.

PD-1hiICOShi CD4+ cells also peaked after hepatitis A virus infection, but the response was accelerated by several weeks when compared with HCV infection. The PD-1hiICOShi phenotype, and temporal association between the peak response and ALT, may provide markers to guide human studies of CD4+ T cell immunity against HCV and other hepatotropic viruses.

In summary, we describe a third subtype of PLAG family-altered pediatric CNS embryonal tumor characterized by PLAG1 gene fusion, which leads to upregulation of PLAG1 and downstream genes. We therefore propose to rename ET, PLAGL to ET, PLAG (CNS embryonal tumor with PLAG family gene alteration) together with a specification of the respective subtype.

Our findings reveal complex GPR56-mediated biased signaling through the Rho-ROCK-MLC and JAK-STAT3 pathways, highlighting these networks as potential therapeutic targets for modulating distinct tumorigenic phenotypes in human melanoma cells.

HIP1R is a new gene implicated in RA FLS invasiveness and migration, and regulates unique pathways and cell processes relevant to both RA as well as cancer biology. Our study provides new insight into processes implicated in FLS invasiveness, which is relevant for joint damage in RA, and identify new potential gene targets for FLS-specific treatments.

High GPR56 expression is found to be associated with a poor prognosis of ESCC. Downregulation of GPR56 suggests a potential significant predictive value in conjunction with MPR analysis.