Skip to main content

Research Intelligence

ScienceView
Health & Medicine

Targeting peripheral 5-HT 2A R enhances antitumor immunity in colorectal cancer.

| Source: Cell

Cancer remains a leading cause of morbidity and mortality worldwide. While classical psychedelics have been used clinically to treat cancer-associated psychiatric disorders, their impact on tumor progression is unclear. Here, we show that by targeting the serotonin receptor 5-HT 2A R, lysergic acid diethylamide (LSD) enhances CD8 + T cell-mediated antitumor immunity and suppresses colorectal cancer (CRC) growth. To harness this activity while avoiding psychedelic effects, we developed IHCH-8110,

Cancer remains a leading cause of morbidity and mortality worldwide. While classical psychedelics have been used clinically to treat cancer-associated psychiatric disorders, their impact on tumor progression is unclear. Here, we show that by targeting the serotonin receptor 5-HT 2A R, lysergic acid diethylamide (LSD) enhances CD8 + T cell-mediated antitumor immunity and suppresses colorectal cancer (CRC) growth. To harness this activity while avoiding psychedelic effects, we developed IHCH-8110, a non-brain-penetrant 5-HT 2A R agonist that selectively targets peripheral 5-HT 2A R. We show that IHCH-8110 inhibits CRC progression by activating 5-HT 2A R on enteric glial cells, thereby inducing CXCL10 and interleukin (IL)-18 expression to promote CD8 + T cell recruitment and effector polarization within the tumor microenvironment. By converting immune-cold CRC into a more immunologically responsive state, IHCH-8110 enhances the efficacy of PD-1 blockade. Together, our findings identify enteric 5-HT 2A R signaling as a regulator of antitumor immunity and support peripheral 5-HT 2A R agonists as a therapeutic strategy for CRC immunotherapy.

Read the original source →

Related Topics

Related Stories

Health & Medicine

Palmitoylation of TK1 exacerbates osteoarthritis by promoting JNK-mediated metabolic reprogramming.

Osteoarthritis (OA) lacks approved disease-modifying therapies. Here, by integrating quantitative proteomics with reanalysis of public single-cell RNA sequencing data from human articular cartilage, we identify thymidine kinase 1 (TK1) as a pathogenic regulator linking inflammatory stress to metabolic rewiring and matrix breakdown. TK1 is markedly upregulated in OA chondrocytes. Mechanistically, IL-1β enhances S-palmitoylation of TK1 at Cys153, which promotes USP9X-dependent deubiquitinati

Continue reading
Health & Medicine

Duration of Therapeutic Hypothermia After Out-of-Hospital Cardiac Arrest: The ICECAP Randomized Clinical Trial.

Therapeutic hypothermia is widely used for neuroprotection following cardiac arrest, but clinical trials have not consistently demonstrated improved neurological outcomes, and the optimal duration of cooling remains uncertain. To determine the duration of therapeutic hypothermia that maximizes neurological recovery in comatose survivors of out-of-hospital cardiac arrest. Multicenter, randomized, adaptive-allocation clinical trial conducted at 71 hospitals in the US. Adults with out-of-hospital c

Continue reading
Health & Medicine

Cryoelectron tomography reveals an age-related decline in mitoribosomes that contributes to T cell dysfunction in older individuals.

Mitochondrial dysfunction drives T cell aging in mice. Yet, due to fundamental differences in T cell aging mechanisms between species, whether human T cells exhibit similar mitochondrial alterations remains unclear, with existing evidence often conflicting. Using cryoelectron tomography, we resolved the structure and spatial organization of mitochondrial ribosomes in primary human CD8 + T cells under physiological conditions. Comparative analysis with human aging models revealed an age-related r

Continue reading
Health & Medicine

RelB NF-κB tunes Notch2 signaling to promote IL-23-secreting solitary isolated lymphoid tissue-resident DCs critical for gut immunity.

While preserving tolerance toward commensals, dendritic cells (DCs) also orchestrate response against pathogens. The noncanonical RelB NF-κB pathway in DCs curbs tolerogenic Tregs in the intestine. Whether RelB-dependent DC regulations also impact intestinal immunity remains less clear. Here, we show that genetic ablation of RelB in DCs compromises IL-23-dependent immune response in the intestine, imparting vulnerability in Relb ΔCD11c mice to infection with Citrobacter rodentium , a

Continue reading
Health & Medicine

X-linked SYTL4 missense variant disrupts RAB27A-dependent vesicle trafficking and synaptic transmission in autism.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive behaviors, with genetic studies implicating widespread synaptic dysfunction. However, the contribution of presynaptic vesicle trafficking mechanisms to ASD pathogenesis remains incompletely understood. Here, we identify synaptotagmin-like protein 4 (SYTL4), a RAB27A effector previously characterized in secretory cells, as a regulator of presynaptic function in the mammal

Continue reading