Scholarlink

Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Integrative analysis of immunogenic PANoptosis and experimental validation of cinobufagin-induced activation to enhance glioma immunotherapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月3日

查看全文
  • Yonghua Cai,
  • Heng Xiao,
  • Shuaishuai Xue,
  • Peng Li,
  • Zhengming Zhan,
  • Jie Lin,
  • Zibin Song,
  • Jun Liu,
  • Wei Xu,
  • Qixiong Zhou,
  • Songtao Qi,
  • Xi’an Zhang,
  • Ziyi Luo

摘要

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.