We demonstrated that the cytoskeletal protein TAGLN2 critically regulates fatty acid uptake, mitochondrial respiration, and effector function in intratumoral T cells (Nature, 2024). Building on this discovery, we are pioneering the concept of cytometabolism—a framework that explores how cytoskeletal elements orchestrate metabolic pathways and, in turn, shape key aspects of T cell biology, including differentiation, persistence, function, and fate. This cytometabolic perspective provides a foundation for engineering next-generation CAR T cells with enhanced metabolic fitness and structural resilience, specifically tailored to withstand the hostile tumor microenvironment.

Visceral adipose tissue (VAT) expands dramatically in obesity, reshaping the immunometabolic landscape of the peritoneal cavity (PC). We propose that the VAT–PC axis plays a critical role in cancer metastasis. From this perspective, we aim to investigate how obesity reshapes the composition and function of T cells within the peritoneal cavity and how these obesity-driven immune alterations influence the metastatic niche. In cancers such as ovarian and colorectal cancer, increased VAT is linked to worse clinical outcomes. Our research focuses on understanding how VAT-driven signals impair T cell function and contribute to tumor progression and metastasis, with the goal of identifying strategies to restore effective immunity within fat-enriched tumor niches.

Progenitor exhausted T cells (Tpex) serve as a critical reservoir that sustains long-term immune responses and responsiveness to immunotherapy. Our research investigates how intrinsic and extrinsic cues—encompassing microenvironmental stressors, metabolic pressures, and structural regulatory pathways—govern the maintenance, differentiation, and functional plasticity of Tpex cells within the tumor microenvironment. By dissecting these molecular and cellular mechanisms, we aim to uncover strategies that preserve the stem-like potential of Tpex cells, delay terminal exhaustion, and promote durable anti-tumor immunity. These insights will inform the development of next-generation immunotherapies that more effectively harness the regenerative capacity of the Tpex compartment.