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Integrative analysis of immunogenic PANoptosis and experimental validation of cinobufagin-induced activation to enhance glioma immunotherapy
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Integrative analysis of immunogenic PANoptosis and experimental validation of cinobufagin-induced activation to enhance glioma immunotherapy
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Journal Article
Integrative analysis of immunogenic PANoptosis and experimental validation of cinobufagin-induced activation to enhance glioma immunotherapy
2025
Overview
Background
Glioma, particularly glioblastoma (GBM), is a highly aggressive tumor with limited responsiveness to immunotherapy. PANoptosis, a form of programmed cell death merging pyroptosis, apoptosis, and necroptosis, plays an important role in reshaping the tumor microenvironment (TME) and enhancing immunotherapy effectiveness. This study investigates PANoptosis dynamics in glioma and explores the therapeutic potential of its activation, particularly through natural compounds such as cinobufagin.
Methods
We comprehensively analyzed PANoptosis-related genes (PANoRGs) in multiple glioma cohorts, identifying different PANoptosis patterns and constructing the PANoptosis enrichment score (PANoScore) to evaluate its relationship with patient prognosis and immune activity. Cinobufagin, identified as a PANoptosis activator, was evaluated for its ability to induce PANoptosis and enhance anti-tumor immune responses both in vitro and in vivo GBM models.
Results
Our findings indicate that high PANoScore gliomas showed increased immune cell infiltration, particularly effector T cells, and enhanced sensitivity to immunotherapies. Cinobufagin effectively induced PANoptosis, leading to increased immunogenic cell death, facilitated tumor-associated microglia/macrophages (TAMs) polarization towards an M1-like phenotype while augmenting CD4+/CD8 + T cell infiltration and activation. Importantly, cinobufagin combined with anti-PD-1 therapy exhibited significant synergistic effects and prolonged survival in GBM models.
Conclusions
These findings highlight the therapeutic potential of PANoptosis-targeting agents, such as cinobufagin, in combination with immunotherapy, offering a promising approach to convert “cold” tumors into “hot” ones and improving glioma treatment outcomes.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Biomedical and Life Sciences
/ Brain Neoplasms - drug therapy
/ Brain Neoplasms - immunology
/ Bufanolides - therapeutic use
/ Ethylenediaminetetraacetic acid
/ Genes
/ Genomes
/ Glioma
/ Gliomas
/ Humans
/ Kinases
/ Mice
/ Oncology
/ Proteins
/ T cells
/ Tumor immune microenvironment
/ Tumor Microenvironment - drug effects
/ Tumors
