非霍奇金淋巴瘤中治疗诱导的细胞衰老，重点关注侵袭性 B 细胞亚型：分子机制与新兴药物靶点

TIS is initiated by persistent DDR signaling (ATM/ATR CHK1/CHK2) with downstream activation of p53-p21 and/or p16^INK4a^-RB pathways, resulting in stable growth arrest. Senescent lymphoma cells may acquire a SASP that remodels the tumor microenvironment and modulates immune responses. Epigenetic reprogramming (e.g., SAHF formation, H3K9me3 dynamics, lamin B1 loss) supports phenotypic plasticity and may enable escape from senescence with stem-like features, contributing to residual dis-ease persistence and relapse biology. DISCUSSION: Therapeutically, senolytic approaches (e.g., BH3 mimetics, BCL-2/BCL-xL antagonists) and senomorphic strategies (targeting SASP regulators such as NF- B, JAK/STAT, and mTOR) represent potentially actionable therapeutic approaches. Emerging senolytic Chimeric Antigen Receptor T-cell (CAR-T cell) strategies targeting senescence-associated surface programs, such as uPAR, further expand the therapeutic landscape, although these approaches remain at a preclinical stage at the time of writing this review.

In lymphomas, TIS is a dynamic stress-adaptation state that can support persistence and relapse. Rational integration of senescence biomarkers, timing-based therapies, and targeted senolytic/senomorphic interventions may enhance long-term treatment efficacy; however, most senescence-targeted strategies remain investigational and require lymphoma-specific clinical validation.