supports mitochondrial dynamics and immune evasion to CD8 T cell in lung adenocarcinoma.

Background: Mitochondrial fusion and fission were identified to play key roles during multiple biology process. Thus, we aim to investigate the roles of OPA1 in mitochondria fusion and immune evasion of non-small cell lung cancer cells.

Methods: The transcriptional activation of genes related to mitochondrial dynamics was determined by using multi-omics data in lung adenocarcinoma (LUAD). We elucidated the molecular mechanism and roles of OPA1 promoting lung cancer through single-cell sequencing and molecular biological experiments.

Results: Here, we found that copy number amplification of and were co-occurring and synergistically activated in tumor epithelial cells in lung cancer tissues. Both of and were highly expressed in LUAD tumor tissues and high expression was associated with poor prognosis. In terms of mechanism, the damaged mitochondria activated the apoptotic signaling pathways, inducing cell cycle arrest and cell apoptosis. More interestingly, OPA1 deficiency damaged mitochondrial dynamics and further blocked the respiratory function to increase the sensitivity of tumor epithelial to CD8 T cells in non-small cell lung cancer.

Conclusions: Our study demonstrated the high co-occurrence of copy number amplification and co-expression of and in LUAD tissue, and further revealed the contribution of OPA1 in maintaining the mitochondria respiratory function and the ability of immune evasion to CD8 T cells of LUAD.