Lung cancer is the deadliest malignancies worldwide. Among its subtypes, non-small cell lung cancer (NSCLC) is the most common pathological phenotype, and its treatment primarily relies on surgery, chemoradiotherapy, targeted therapy, and immunotherapy. In recent years, immunotherapy has shown unique advantages in controlling NSCLC progression, but its efficacy is heavily restricted by T-cell exhaustion within the tumor microenvironment. The T-cell exhaustion involves multidimensional mechanisms including continuous antigen stimulation, imbalanced cytokines, transcriptional regulation abnormalities, epigenetic modifications, and chromosomal structural remodeling, which has become a focal point in tumor immunology research. Studies targeting T-cell exhaustion mechanisms are considered to hold potential for overcoming current immunotherapy limitations. This review systematically summarizes the recent clinical and fundamental research advances on T-cell exhaustion in NSCLC, aiming to provide insights for further understanding the immune evasion mechanisms of NSCLC and to inform the development of novel immunotherapy strategies.

Objective: To investigate the expression pattern and clinical significance of myosin heavy chain 9 (MYH9) in pancreatic cancer, and its potential mechanism in regulating the sensitivity to FOLFIRINOX regimen.

Methods: Based on the public databases including TCGA (The Cancer Genome Atlas), GTEx (Genotype-Tissue Expression) and GEO (Gene Expression Omnibus), we analyzed the expression pattern of MYH9 gene in pancreatic cancer patients and its relationship with patient prognosis using the online platforms GEPIA (Gene Expression Profiling Interactive Analysis) and UALCAN (The University of Alabama at Birmingham Cancer Data Analysis Portal). The changes of the sensitivity of pancreatic cancer cells to FOLFIRINOX regimen were evaluated by interfering the expression of MYH9 gene in vitro. Further, we investigated the potential mechanism of MYH9 regulating the sensitivity of pancreatic cancer cells to FOLFIRINOX regimen using immunofluorescence and Gene Set Enrichment Analysis (GSEA).

Results: The expression of MYH9 gene was significantly upregulated in pancreatic cancer tissues, and its high expression was closely associated with poor prognosis in pancreatic cancer patients. Plate colony formation assay demonstrated that MYH9 knockdown enhanced the sensitivity of pancreatic cancer cells to FOLFIRINOX regimen. Immunofluorescence staining results suggested that alterations in DNA damage levels may be a critical mechanism through which MYH9 influences the sensitivity of pancreatic cancer cells to FOLFIRINOX regimen. GSEA and correlation analysis further revealed that abnormal activation of the NOTCH signaling pathway may be a potential mechanism by which MYH9 affects DNA damage in pancreatic cancer cells.

Conclusion: MYH9 is abnormally highly expressed in pancreatic cancer tissues and is closely related to poor prognosis in pancreatic cancer patients. MYH9 may regulate the activation of NOTCH signaling pathway to influence the DNA damage level in pancreatic cancer cells, thereby regulating the sensitivity of pancreatic cancer cells to FOLFIRINOX regimen.