Reading view
Ferritin aggregation cell engager for CAR T avidity engineering against refractory leukemias
Structure of the mouse cytoplasmic lattice
Nature, Published online: 31 March 2026; doi:10.1038/s41586-026-10442-6
Structure of the mouse cytoplasmic latticeCellular Senescence in Gastric Cancer: Molecular Mechanisms, Microenvironment Remodeling and Therapeutic Implications
Aging Dis. 2026 Mar 19. doi: 10.14336/AD.2025.1571. Online ahead of print.
ABSTRACT
Gastric cancer (GC) remains a leading cause of cancer-related morbidity and mortality worldwide, with poor prognosis for advanced-stage patients. Therefore, in-depth exploration of the mechanisms underlying GC initiation and progression, as well as the development of novel therapeutic strategies, is of crucial importance. Cellular senescence is a stable cell cycle arrest program that plays a dual role in GC. It exerts tumor-suppressive effects via growth arrest but also promotes tumor progression and immune evasion by remodeling the tumor microenvironment (TME) through senescence-associated secretory phenotype (SASP). This review comprehensively elucidates the molecular mechanisms of cellular senescence in GC and the core regulatory networks involving gene regulation, epigenetic modifications, metabolic reprogramming, and cell cycle arrest. Additionally, the review highlights how senescent cells foster an immunosuppressive microenvironment via SASP, forming a self-reinforcing feed-forward loop. Regarding therapeutic strategies, we summarize potential approaches targeting cellular senescence, including senescence induction, senescent cell clearance, SASP modulation, and multi-target synergistic therapy by integrating epigenetic regulation, metabolic intervention, and immune microenvironment modulation. Despite progress, numerous challenges remain. Future studies should leverage multi-omics technologies, novel models' development, and large-scale clinical trials to advance the clinical translation of GC cellular senescence research, providing new insights for improving prognosis.
PMID:41910653 | DOI:10.14336/AD.2025.1571
The Yin and Yang of tertiary lymphoid structures in primary liver cancer
Cancer Lett. 2026 Mar 27;648:218461. doi: 10.1016/j.canlet.2026.218461. Online ahead of print.
ABSTRACT
Tertiary lymphoid structures (TLSs) have emerged as key regulators of anti-tumor immunity and biomarkers for immunotherapy response in liver cancer, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and combined hepatocellular-cholangiocarcinoma (cHCC-iCCA). Advances in single-cell and spatial multi-omics technologies have revealed unprecedented complexity in TLSs, challenging the traditional binary classification of TLSs as simply "good" or "bad". Their functional diversity appears to be shaped by spatiotemporal context, cellular composition, and maturation status. This review provides a comprehensive synthesis of TLSs in liver cancer, employing the Yin-Yang paradigm to navigate their functional dualism and prognostic contradictions through a detailed analysis of their identification, classification, and spatiotemporal interactions within the TME. Mechanistically, we elucidate how TLS functions are orchestrated by complex interactions between tumor cells, immune cell subsets, stromal components, and systemic factors. Within this framework, key metabolic drivers, notably ATP citrate lyase (ACLY), and signaling axes such as cGAS-STING/mTOR have emerged as pivotal regulators of TLS ontogeny. In addition, we evaluate current preclinical animal models and therapeutic strategies for clinical TLS induction. Furthermore, we have discussed the key unanswered questions in the field, including the three-dimensional architecture of TLSs and the mechanisms by which they establish durable immunological memory independent of the primary tumor. Clinically, TLSs exhibit great promise as prognostic and predictive biomarkers, particularly in the context of immune checkpoint blockade and locoregional therapies. Finally, we identify challenges in standardization, mechanistic understanding, and translational applications, providing directions for future research to harness TLSs for improving liver cancer outcomes.
PMID:41905709 | DOI:10.1016/j.canlet.2026.218461