Unraveling the link between genomic instability and tumor immune evasion in oral squamous cell carcinoma: Role of CBMN assay and emerging perspectives
摘要
Oral squamous cell carcinoma (OSCC), being the most common malignancy of head and neck origin, corelates with genomic instability (GI) through increased consumption of carcino-genotoxic substances. Elevated consumption of tobacco, betel quid, araca nut, alcohol, pipe and cigarette smoking predispose the cells to persistent DNA damage and chromosomal abnormalities. GI leads to tumor immune evasion by suppression of immune signaling pathways (PI3K/AKT/mTOR, RAS/RAF/MAPK, cGAS-STING), upregulation of exhaustion markers (PD-1, CTLA-4), and T-regs (FOXP3) followed by downregulation of cytokine secretion (SOC3) and Major Histocompatibility Complex-1 (MHC-I). Cytokinesis block micronucleus (CBMN) assay is a cost-effective cytogenetic test that efficiently quantifies various metrices of GIg (micronucleus, nuclear buds, nucleoplasmic bridge frequency and chromosomal abrasions), cell proliferation/stasis (replication index, cytokinesis block proliferation index, cytostasis percentage, nuclear division index, nuclear division cytotoxicity index and disturbed ana-telophase) and cell death (apoptotic and necrotic percentage). Therefore, the utilization of CBMN assay for the cytogenetic assessment of peripheral blood mononuclear cells could offer promising results for the accurate quantification tumor immune evasion. Additionally, the review aims to deliver a novel insight into GI-TIE axis and a proposed GI-TIE index to relate GI with TIE severity in OSCC patients. The precise quantification of various cytogenetic metrices for the quantification of tumor immune evasion usingCBMN assay has translational potential to enhance personalized medicine and precision oncology.