Ionic tumor immune regulation

Ions play a vital role in regulating the antitumoral functions of immune cells within the tumor microenvironment (TME). Protons, derived from endogenous lactic acid or external sources (such as acetate), significantly affect tumor or immune cell function by altering the metabolic pathways of tumor or immune cells. Along with sodium and calcium, these ions are involved in electrochemical communications between tumor-to-tumor and tumor-to-neurons, modulating malignant initiation, growth, and metastasis through paracrine signaling. Additionally, essential nutritional metal ions—including sodium, lithium, magnesium, calcium, zinc, iron, copper, manganese and selenium—are crucial for promoting the maturation and activation of antigen-presenting cells (APCs) and sustaining the antitumoral functions of tumor resident immune cells.Deficiency in these ions has been shown to impair the antitumoral activity of immune cells. Moreover, several of these ions are intricately linked to ferroptosis, cuproptosis, necroptosis, and pyroptosis in tumor cells, influencing immune responses and tumor survival. Recent achievements have witnessed tremedous progress in the field of metalloimmunotherapy. Therefore, this topic issue will undoubtly attratct researchers from materials science, immunology, pharmacology, oncology and chemistry.