T cell senescence is a critical factor in the dysfunction of the immune system, particularly in the context of lung cancer. Senescent T cells exhibit reduced responsiveness to cognate antigens, leading to ineffective tumor cell clearance and the formation of a suppressive tumor microenvironment (TME). This review discusses the characteristics, mechanisms, and expression of T cell senescence in malignant lung tumors, emphasizing its impact on immunotherapy efficacy. Key aspects include: 1. **Characteristics of T Cell Senescence**: - Morphological changes: flatter and larger cells. - High expression of age-related β-galactosidase (SA-β-gal), telomere shortening, and genomic instability. - Low expression of CD27 and CD28 costimulatory molecules. - High expression of KLRG1 and CD57. - Production of pro-inflammatory factors like IL-2, IL-6, IL-8, IFN-γ, and TGF. 2. **Mechanisms of T Cell Senescence**: - Activation of age-related pathways: MAPK signaling, cAMP, and DNA damage. - Telomere shortening: loss of telomerase activity and genomic instability. - Mitochondrial dysfunction: impaired mitochondrial function and reactive oxygen species (ROS) production. - Inflammatory stimulation: chronic inflammation and SASP factors. 3. **Role of Senescent T Cells in Malignant Tumors**: - Promotion of immune escape and tumor growth through SASP factors. - Inhibition of T cell proliferation and function. - Induction of adaptive Tregs and promotion of pro-inflammatory factors. 4. **Therapeutic Strategies**: - Blocking key signaling pathways: p38, ERK, JNK, and STAT. - Enhancing mitochondrial function: iron supplementation and NAD+ levels. - Maintaining telomere length: targeting telomerase and ALT mechanisms. - Anti-inflammatory therapy: targeting immunosuppressive cells and cytokines. The review highlights the importance of understanding and reversing T cell senescence to enhance the efficacy of immunotherapies in lung cancer. Key targets include the MAPK and TLR8 signaling pathways, which can effectively control T cell senescence and improve immunotherapy outcomes.T cell senescence is a critical factor in the dysfunction of the immune system, particularly in the context of lung cancer. Senescent T cells exhibit reduced responsiveness to cognate antigens, leading to ineffective tumor cell clearance and the formation of a suppressive tumor microenvironment (TME). This review discusses the characteristics, mechanisms, and expression of T cell senescence in malignant lung tumors, emphasizing its impact on immunotherapy efficacy. Key aspects include: 1. **Characteristics of T Cell Senescence**: - Morphological changes: flatter and larger cells. - High expression of age-related β-galactosidase (SA-β-gal), telomere shortening, and genomic instability. - Low expression of CD27 and CD28 costimulatory molecules. - High expression of KLRG1 and CD57. - Production of pro-inflammatory factors like IL-2, IL-6, IL-8, IFN-γ, and TGF. 2. **Mechanisms of T Cell Senescence**: - Activation of age-related pathways: MAPK signaling, cAMP, and DNA damage. - Telomere shortening: loss of telomerase activity and genomic instability. - Mitochondrial dysfunction: impaired mitochondrial function and reactive oxygen species (ROS) production. - Inflammatory stimulation: chronic inflammation and SASP factors. 3. **Role of Senescent T Cells in Malignant Tumors**: - Promotion of immune escape and tumor growth through SASP factors. - Inhibition of T cell proliferation and function. - Induction of adaptive Tregs and promotion of pro-inflammatory factors. 4. **Therapeutic Strategies**: - Blocking key signaling pathways: p38, ERK, JNK, and STAT. - Enhancing mitochondrial function: iron supplementation and NAD+ levels. - Maintaining telomere length: targeting telomerase and ALT mechanisms. - Anti-inflammatory therapy: targeting immunosuppressive cells and cytokines. The review highlights the importance of understanding and reversing T cell senescence to enhance the efficacy of immunotherapies in lung cancer. Key targets include the MAPK and TLR8 signaling pathways, which can effectively control T cell senescence and improve immunotherapy outcomes.