Activated T cells induce apoptosis in A549 lung adenocarcinoma cells via TRPV4-mediated calcium influx.

Lung cancer remains the most commonly diagnosed malignancy worldwide and is a leading cause of cancer-related mortality. Conventional therapies, including chemotherapy and radiotherapy, are often limited by treatment resistance and disease recurrence, highlighting the need for alternative approaches such as immunotherapy. In this study, we investigated the pro-apoptotic effects of activated T cells on A549 lung cancer cells, with a particular focus on TRPV4-mediated calcium signaling. A549 cells were co-cultured with Jurkat T cells in the presence of calcium to evaluate T cell-mediated cytotoxicity. Cell viability was assessed using the MTT assay at 24 and 72 h, while apoptosis and necrosis were quantified by Annexin V staining and flow cytometry. T cell activation was confirmed through immunophenotyping for CD3 expression. We further evaluated oxidative stress markers, including total antioxidant capacity (TAC) and total oxidant status (TOS), alongside TRPV4 protein expression. Activated T cells significantly decreased A549 cell viability in a dose-dependent manner. Notably, calcium alone enhanced cell viability, whereas its combination with activated T cells markedly increased cytotoxicity and necrosis. TRPV4 expression was upregulated in cells treated with both calcium and activated T cells, suggesting a key role in mediating calcium influx and subsequent apoptosis. Additionally, combinatorial treatment led to decreased TAC and elevated TOS levels, indicating enhanced oxidative stress. These findings reveal a novel immunotherapeutic mechanism whereby activated T cells induce apoptosis through TRPV4-dependent calcium signaling, offering a potential strategy to improve lung cancer treatment efficacy. Further studies are warranted to elucidate the modulation of calcium pathways in T cell-driven anti-tumor responses.