Ischemia and reperfusion injury combined with cisplatin induces immunogenic cell death in lung cancer cells.
Shuai ZhangYumei LiShuqing LiuPei MaMengfei GuoE ZhouLimin DuanJinshuo FanTingting LiaoQi TanXuan WangFeng WuYang JinPublished in: Cell death & disease (2022)
A first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), cisplatin (CDDP), fails to induce immunogenic cell death (ICD) because it fails to induce calreticulin (CRT) exposure on the cell surface. We investigated the potential of ischemia and reperfusion injury (I/R) combined with CDDP to induce ICD in lung cancer cells. The in vitro model of I/R, oxygen-glucose deprivation and reperfusion (OGD/R), effectively induced CRT exposure, ATP secretion, high mobility group box 1 (HMGB1) release and eIF2α phosphorylation in both Lewis lung carcinoma (LLC) and A549 cells when combined with CDDP. By using a vaccine assay and coculture with bone marrow-derived dendritic cells (BMDCs), we showed that OGD/R restored the immunogenicity of CDDP by phosphorylating eIF2α and demonstrated that OGD/R + CDDP (O + C) is an ICD inducer. Using the inguinal tumor model, we found that I/R significantly enhanced the tumor-killing effect of CDDP and Mitomycin C, and this effect relied on adaptive antitumor immunity. Consistently, I + C altered the ratio of interferon-gamma-secreting T lymphocytes, thus overcoming the immunosuppressive effect induced by CDDP. In conclusion, our research presents a new combination strategy and indicates that I/R is a potential anticancer immunogenic modality when combined with nonimmunogenic chemotherapy.
Keyphrases
- cell death
- dendritic cells
- cell cycle arrest
- acute myocardial infarction
- cerebral ischemia
- cell surface
- small cell lung cancer
- acute ischemic stroke
- induced apoptosis
- immune response
- heart failure
- type diabetes
- bone marrow
- mesenchymal stem cells
- transcription factor
- coronary artery disease
- regulatory t cells
- mass spectrometry
- emergency department
- signaling pathway
- cardiac resynchronization therapy
- oxidative stress
- percutaneous coronary intervention
- adipose tissue
- left ventricular
- advanced non small cell lung cancer
- climate change
- human health
- blood pressure
- atrial fibrillation
- binding protein
- locally advanced
- subarachnoid hemorrhage
- radiation therapy
- electronic health record
- adverse drug
- tyrosine kinase