Immunosenescence in tumor progression: from synergistic mechanisms to therapeutic strategies.

Tumor-associated immunosenescence is not a decline in immune function, but rather a state of immune ecological imbalance. It drives tumor progression through multi-dimensional mechanisms, including decreased immune surveillance, chronic inflammation, accumulation of suppressive cells, remodeling of TME, metabolic disorders, and epigenetic regulation. The challenges in immunosenescence research include conceptual confusion, an imbalance in research perspectives, the limitations of preclinical models, and the translational hurdles. This review summarizes the latest research findings on the role of immunosenescence in tumor progression and its multiple regulatory mechanisms and highlights the promise of targeted therapeutic strategies against immunosenescence. The synergy among multiple mechanisms of immunosenescence creates a self-reinforcing cycle of chronic inflammation and immune dysfunction, thereby driving immune ecological imbalance. The core strategies of targeted therapy for immunosenescence include eliminating or regulating senescent immune cells to rejuvenate the immune system, as well as enhancing the immune system's ability to clear senescent cells, thereby achieving immune ecosystem remodeling. Future research should focus on deciphering the deep heterogeneity of immunosenescence, elucidating the mechanisms of key overlapping processes such as T-cell exhaustion, developing clinical tools for precise assessment of immune age, optimizing preclinical models, and conducting innovative "immune age-oriented" clinical trials.