Recent advances in pH-sensitive clay nanomaterials for enhanced immunotherapy of solid tumors

The tumor microenvironment is a formidable barrier, complicated by physicochemical malice to the immune system, limiting the clinical efficacy of immunotherapy, particularly CAR-T, in solid tumor management. Various strategies have been proposed and examined to enhance immunotherapy, while the aberrant and hostile physicochemical microenvironment (such as low pH, hypoxia, high ROS/RNS and deficient nutrient ions) is always a key and general challenge that must be addressed in order to improve the efficacy of CAR-T and immune checkpoint blockage for solid tumor treatment. Fortunately, recent investigations demonstrate that some clay nanomaterials are able to correct aberrant pH and O₂ levels in the tumor microenvironment and recruit more anti-tumor immune cells into tumor tissues, breaking the immunosuppressive barrier and inhibiting tumor growth in vivo. This minireview briefly summarizes the timely progress in restoring the physicochemical homeostasis in tumor tissues to convert the 'cold' immune microenvironment to a 'hot' one for enhanced immunotherapy of solid tumors and further provides my personal perspectives for future research.