• CAR-T therapy faces challenges in solid tumors; strategies like optimizing receptor clustering and co-stimulatory domains are proposed to enhance efficacy.
• Reductive stress and PRR signaling in T cells are emerging as critical modulators of immune responses, offering new therapeutic targets.
• Neurotransmitters and circadian rhythms significantly influence T cell function and immunotherapy outcomes, suggesting chronobiological and neuro-immune interventions.
• Innate immune cells (ILC2s, macrophages) and their crosstalk with T cells are central to homeostasis and disease, with lipid metabolism emerging as a key regulator.