Ageing, immune fitness and cancer.

The immune system undergoes substantial changes throughout life, with ageing broadly impacting immune cell composition, function and regenerative capacity. Emerging evidence suggests that age-associated changes in immune fitness - the ability to respond to and eliminate infection, pathogens and malignancy while maintaining self-tolerance - reshape antitumour immunity and influence the efficacy of immunotherapies. Technological advances in high-dimensional immunoprofiling have begun to reveal the complex interplay between ageing, immune fitness and cancer biology, uncovering new therapeutic vulnerabilities and challenges.

The physical landscape of CAR-T synapse.

Chimeric antigen receptor (CAR)-T cells form dynamic immunological synapses with their cancer cell targets. After a CAR-antigen engagement, the CAR-T synapse forms, matures, and finally disassembles, accompanied by substantial remodeling of cell surface proteins, lipids, and glycans. In this review, we provide perspectives for understanding protein distribution, membrane topology, and force transmission across the CAR-T synapse.

Rewired signaling network in T cells expressing the chimeric antigen receptor (CAR).

The chimeric antigen receptor (CAR) directs T cells to target and kill specific cancer cells. Despite the success of CAR T therapy in clinics, the intracellular signaling pathways that lead to CAR T cell activation remain unclear. Using CD19 CAR as a model, we report that, similar to the endogenous T cell receptor (TCR), antigen engagement triggers the formation of CAR microclusters that transduce downstream signaling.

Imaging Chimeric Antigen Receptor (CAR) Activation.

The chimeric antigen receptor (CAR) has been extensively exploited in cancer immunotherapy. In spite of the success of CAR T cells in clinical applications, the molecular mechanism underlying CAR-T cell activation remains unclear. Key questions remain: how are CARs activated by tumor antigens? How do activated CARs transduce signaling to downstream pathways? Here we introduce a microscopy-based method for studying CAR signaling.