CD200R1 (CD200 Receptor 1)

Targeting the CD200-mediated dormant niche in combination with chemotherapy and immune check point blockade (ICB) significantly eradicated the dormant tumor cells. These insights provide mechanistic understanding of tumor dormancy and treatment options for ICB relapse.

The obtained results confirm an increased immunoactivation profile in children with VLS, characterized by elevated checkpoint expression and increased levels of proinflammatory cytokines. The studied parameters show potential as diagnostic and prognostic biomarkers, which may constitute the basis for the development of new diagnostic tools and targeted therapeutic strategies in VLS in pediatric patients.

Although CD200R1 is not expressed by adult γδ T cells, it is expressed by immature developing γδ T cells in foetal thymus where it supports the development of γδ17 T cells, enhancing IL-17-producing and RORγt+ γδ T cell numbers in foetal thymic organ cultures. This identifies CD200R1 as an important novel regulator of γδ17 T cell development in early life, a key process for ensuring immunity, particularly at barrier sites.

Our study delineates a comprehensive immune checkpoint-ligand network encompassing seven novel ICs and 46 associated ligands, providing mechanistic insight into Treg- and T cell-mediated immune regulation. This expanded IC landscape broadens the current repertoire of immune modulatory pathways and highlights new therapeutic opportunities across cancer, autoimmune disorders, infectious diseases, transplantation immunology, inflammatory conditions, and cardiovascular diseases.

Functionally, IL-27 blockade accelerated tumor growth, whereas recombinant IL-27 restrained tumor progression and enhanced PD-L1/CTLA-4 blockade efficacy by augmenting Th1 and cytotoxic T cell responses. These findings define a TME-based prognostic classifier and position IL-27 as a stage-dependent therapeutic target that restores T cell immunity and boosts checkpoint blockade efficacy.

Notably, neuronal synapses are primary targets of such inflammation-driven dysfunction, where prolonged exposure to cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and signaling via receptor systems including cluster of differentiation-200 (CD200)/CD200 receptor (CD200R), C-X3-C motif chemokine ligand 1 (CX3CL1)/CX3C receptor 1 (CX3CR1), colony-stimulating factor 1 (CSF1)/CSF1 receptor (CSF1R), and interferon-γ (IFN-γ)/IFN-γ receptor (IFN-γR), lead to impaired learning, excitotoxicity, and neurodegenerative progression. This review synthesizes emerging evidence on the mechanisms by which microglia-mediated immune responses regulate synaptic remodeling, emphasizing the roles of pro-inflammatory cytokines and their receptors in neurodegenerative disorders.

Homeostatic conditioning and effector cooperativity between CD8+T and NK cells protect against tumor immune escape. The findings uncover a mechanistic axis of preemptive immunosurveillance that lays the foundation for next-generation preventive immunotherapies to control antigen-escape tumors.

In vitro experiments revealed that most of the seven ERGs were overexpressed in LUAD cells, and that SEMA7A knockdown could suppress LUAD cell proliferation, migration and invasion. Our results provided novel insights for the prognosis prediction and personalized treatment of LUAD.

The immunostimulatory properties of BOC1 observed in vitro are compatible with an ICI-like behavior of this bacterial protein. Given that neither the CD200 protein nor the anti-CD200 antibody is able to compete with BOC1 for binding to CD200R1, and as supported by AlphaFold modeling predictions, CD200 and BOC1 might target different regions of CD200R1.

Notably, PD-L1 appears to be more enriched on exosomes than on tumor cell surfaces, underscoring the pivotal role of BEXs in immune regulation. Given their influence on several hallmarks of cancer, BEXs are promising candidates for future diagnostic and therapeutic strategies, particularly in immunotherapy.

Finally, we demonstrated that inhibition of CD200 increase response to Daratumumab in MM patient samples, highlighting its potential as a predictive biomarker for Daratumumab response and as a possible therapeutic target in combination with Daratumumab. This study is the first to identify phenotypic and molecular factors' predictor of response to Daratumumab.

In contrast, terminally differentiated and FcεR1+ CD11c- c-kit- sorted mBaso do not dedifferentiate in mast cells when placed in culture, and responded to IL-33 stimulation by up-regulating the activation marker CD63 without down-modulation of FcεRI and CD200R3. These evidences highlight that in vitro differentiation followed by cell sorting is a useful method to obtain elevated numbers of highly pure mBaso that preserve their lineage markers and thus are suitable for conducting the desired functional studies.